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Managers reports of automated coding system adoption and effects on data quality.

OBJECTIVE: Assessment of the adoption of automated classification (encoder) systems in healthcare settings and related effects on perceived data quality. METHODS: Survey of all U.S. accredited medical records managers, summarizing their reports of automated encoding systems and data quality change following adoption of systems. RESULTS: Significant improvement in data was seen from adoption of automated encoding systems, though variation existed across regions and key demographic variables. CONCLUSION: At a national level, there is a need to minimize data quality variation and ensure some degree of nationwide uniformity in the performance of coding systems. If healthcare providers are expected to trust coded data for comparative purposes, there will be a like need for more uniform and standardized system-based performance benchmarks.

Attitude of Health Personnel↗

Gamma delta T cells assist alpha beta T cells in adoptive transfer of contact sensitivity.

Cutaneous immune responses to contact sensitizers such as picryl chloride or oxazolone, are classical manifestations of T cell-mediated immunity in vivo. In fact, the first documentation of T cell-mediated immunity was the ability to adoptively transfer contact sensitivity (CS) responses. Although it is now clear that Ag/MHC-restricted alpha beta TCR positive effector T cells are responsible for 24 to 48 h CS responses, other subsets of Thy-1+ cells in mice also participate in the elicitation of CS. Thus, Thy-1+, CD5+, CD3-, B220+, hapten-specific, non-MHC-restricted early-acting cells are required to initiate CS responses by leading to local serotonin release, which allows for extravascular recruitment of the late-acting, alpha beta TCR+, CS effector T cells. This study describes another T cell population that is needed for the adoptive transfer of CS by alpha beta T cells. In vitro treatment of a mixture of CS effector cells with hamster mAb to gamma delta TCR, together with rabbit complement, or by panning on anti-hamster Ig-coated dishes, diminished substantially the subsequent transfer of CS reactivity without affecting either CS-initiating cells, or the later-acting, alpha beta TCR+ CS effector T cells. Immune cells treated with anti-alpha beta TCR mAb, or recovered as adherent cells from petri dishes after anti-gamma delta TCR panning (i.e., gamma delta TCR-enriched cells), reconstituted the ability of anti-gamma delta TCR-treated immune cells (i.e., alpha beta TCR-enriched cells) to transfer 24-h CS responsiveness. The phenotype of the gamma delta T cells that assisted CS effector alpha beta T cells was: CD3+, CD4-, and CD8+. The gamma delta T cells that assisted alpha beta T cells were not Ag-specific since anti-alpha beta-TCR-treated cells (gamma delta T-enriched) from picryl chloride immunized donors aided alpha beta T cells (anti-gamma delta TCR-treated) from oxazolone-immunized donors, and conversely gamma delta T cells from oxazolone-immunized donors aided alpha beta T cells from picryl chloride immunized donors. Furthermore, the CS-regulating gamma delta T cells were not MHC-restricted because gamma delta T cells from H2d or H2b donors could assist alpha beta T cells from H2k donors. It was concluded that a regulatory population of non-Ag specific, non-MHC-restricted gamma delta T cells was needed to assist immune effector, Ag/MHC-specific alpha beta T cells in the adoptive transfer of CS.

Animals↗

Report details eRx challenges and provides suggestions for increased adoption.

A new report by the eHealth Initiative (http://www.ehealthinitiative.org) looks at electronic prescribing, or "eRx," and discusses its benefits, challenges to adoption, and movements toward adoption. Released in April 2004, the 154-page report--Electronic Prescribing: Toward Maximum Value and Rapid Adoption--also highlights recommendations for the optimal design of an eRx system.

Diffusion of Innovation↗

Factors that could motivate people to adopt safe hygienic practices in the Eastern Cape Province, South Africa.

BACKGROUND: Approximately 18 million South Africans do not have access to adequate sanitation. This problem is not unique to South Africa but is a challenge to many developing countries. OBJECTIVES: The purpose of this qualitative study was to gain insight and understanding of factors that could motivate people to adopt safe hygienic practices. METHODS: A non-probability purposive sample of 122 participants was drawn from sanitation stakeholder organisations in the Eastern Cape Province. Of these, 74 were male and 48 were female. The mean age of the participants was 40.1 years. The 122 participants were divided into 15 focus groups, each consisting of about eight members. The focus group discussions were conducted using seven guiding questions. Responses were examined and clustered in terms of the primary focus group questions. RESULTS: Regular water supply, provision of sanitation facilities, stakeholder participation and improvement of consumer sanitation knowledge are factors which can motivate people to adopt safe hygienic practices. CONCLUSIONS: There are cultural, educational, economic, institutional, environmental and psycho-social factors that could motivate people to adopt safe hygienic practices.

Adult↗

Workflow analysis in primary care: implications for EHR adoption.

Within busy practice settings, it is difficult to provide adequate provider training on evolving electronic health record (EHR) functionality. As a result, providers may not reap the full benefits of EHR. This poster presents a systematic workflow study conducted to enhance the adoption of advanced EHR features. This study led us to develop new adoption and training strategies, which resulted in statistically significant (p<0.03) improvement in the adoption of advanced results management features.

Computer User Training↗

Human xenograft-nude mouse model of adoptive immunotherapy with human melanoma-specific cytotoxic T-cells.

We investigated the efficacy of human melanoma-specific cytotoxic T-cells (CTLs) in treating experimental human melanoma metastases in a nude mouse model of adoptive immunotherapy. Hepatic metastases were generated by the intrasplenic injection of 1.5 x 10(6) human melanoma cells. Animals were then randomized to receive saline, interleukin-2 only, or CTLs and interleukin-2. CTLs were effective when administered 3 or 7 days after generation of hepatic metastases, with 96 and 88% of animals disease-free, respectively, when examined at one month. Interleukin-2 alone was not effective. In addition, CTLs were effective when as few as 2.5 x 10(6) T-cells were adoptively transferred. Only 33% of the animals were tumor-free when CTLs were administered on day 10, and CTLs were not effective when given at day 14. Human CTLs that were not cytotoxic for the tumor line used in vivo, when tested in a 51Cr assay, were also not effective in the model of immunotherapy. This suggests that the tumor-specific CTLs maintain their specificity in vivo, and eliminates a nonspecific inflammation directed against the human CTLs as a possible cause of the antitumor effect. These studies lay the foundation for clinical trials of CTLs in the adoptive immunotherapy of patients with metastatic melanoma.

Animals↗

Long-term survival of adoptively transferred tumor-infiltrating lymphocytes in mice.

We examined the long term survival of adoptively transferred, cultured tumor-infiltrating lymphocytes (TIL) in sublethally irradiated nontumor-bearing mice. TIL were produced by culturing Thy-1-enriched single cell suspensions from a variety of murine tumors in exogenous IL-2 along with irradiated tumor cells and splenocytes. TIL were adoptively transferred i.v. to mice and such animals demonstrated a statistically significant degree of protection from a subsequent i.v. tumor challenge. This protection lasted up to 6 wk and occurred in the absence of exogenous IL-2 administration in vivo. Using congenic B6.PL Thy-1 alpha/CY mice we demonstrated directly that TIL can survive in vivo for up to 6 wk and that the adoptively transferred TIL were the source of the relative immunity to subsequent tumor challenge. We conclude that TIL contain cells with substantial functional longevity in vivo even in the absence of exogenous IL-2. These studies are relevant to ongoing clinical trials of TIL as a therapy for patients with advanced cancer.

Animals↗

Innovation adoption behavior among nurses.

This study examined the extent of adoption by clinical nurses of 14 research-based nursing practices and explored characteristics of the nurses which may have influenced their use of innovations. The relationship between the nurses' adoption of innovative practices and their perception of organizational support in the form of a hospital policy about the practice was also examined. The 14 nursing practices used in the study met the criteria established by the 1982 Conduct and Utilization of Research in Nursing (CURN) Project. The Nursing Practice Questionnaire (NPQ) developed by Brett (1987) to explore nurses' stage of innovation adoption was sent to a random sample of nurses in 10 medium sized hospitals throughout North Carolina; 113 nurses responded. The majority of the sample were aware of 9 of the 14 nursing practices. The percentage who were aware of individual practices ranged from 28% to 93.8%. Eight of the 14 practices were used regularly by more than half of the sample.

Educational Status↗

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes].

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.

Adult↗

Adoptive immunotherapy of a newly induced sarcoma: immunologic characteristics of effector cells.

A newly induced syngeneic transplantable sarcoma, MCA 105, was used for studies of the biologic characteristics of fresh noncultured and secondarily in vitro sensitized (IVS) cells with antitumor reactivity. Fresh spleen cells harvested from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum exhibited no detectable cytotoxic activity to MCA 105 tumor targets in a 4-hr chromium-release assay, and adoptive transfer of these cells mediated the specific regression of established MCA 105 tumors. Phenotypic analysis of fresh, noncultured immune cells revealed that the therapeutically effective cells expressed both the Lyt-1 and the Lyt-2 T cell differentiation antigens. The therapeutic efficacy of fresh noncultured immune cells was not augmented by the concomitant administration of exogeneous interleukin 2 (IL 2). Secondary IVS of fresh immune cells with irradiated MCA 105 tumor stimulator cells resulted in the generation of tumor-specific cytotoxic effector cells. The generation of cytotoxic effector cells required Lyt-1+, 2+ cytotoxic precursor cells. Effective adoptive immunotherapy with these IVS immune cells, unlike fresh noncultured immune cells, depended on the concomitant administration of IL 2. Furthermore, the generation of therapeutically effective cells did not require the specific stimulation by MCA 105 tumor cells, because cultures of MCA 105 immune spleen cells with FBL-3 lymphoma cells in vitro also contained in vivo functional immune effector cells. These cells, however, possessed no detectable MCA 105 cytotoxic activity in vitro. Although this observation suggests that a noncytotoxic cell population is sufficient to initiate tumor regression in vivo, it does not exclude the possibility that cytolytic cells are generated in vivo after adoptive transfer of these cells. As a whole, our results indicate that secondary IVS functional immune effector cells are characteristically distinct from freshly harvested immune cells.

Animals↗

The in vivo distribution of human peripheral blood lymphocytes and lymphokine-activated killer cells adoptively transferred in human pancreatic cancer-bearing nude mice.

In this study we evaluated human pancreatic cancer xenotransplanted into nude mice as a model suitable for adoptive immunotherapy studies. A pancreatic cancer cell line (MIA PaCa-2) was chosen and its growth in nude mice and sensitivity to lysis by human lymphokine-activated killer (LAK) cells were characterized. This line grew in 96% of the cases when young (4- to 6-week-old) Swiss/NIH nude mice were used. The line was highly sensitive to lysis by LAK cells in a standard chromium-51 release assay (67.8%), similarly to other cell lines known to be highly sensitive, such as K562 (75.6%) and the melanoma cell line SU.102 (53.1%). To assess their in vivo distribution, human peripheral blood lymphocytes (PBLs) and LAK cells were adoptively transferred into nude mice after labeling with indium-111 oxine. The results of this study show that adoptively transferred PBLs and LAK cells localize in this heterologous system as they do in autologous systems. PBLs are taken up mostly by the liver and spleen. The percentage of the administered dose of radioactivity taken up corrected by weight (percent dose per gram tissue) is 64.3 +/- 15.6%d/gm (liver) and 43.5 +/- 9.5%d/gm (spleen). LAK cells are taken up by liver (43.2 +/- 5.3%d/gm) and spleen (28.0 +/- 4.9%d/gm) but also localize significantly more than PBLs in other organs such as lungs (12.9 +/- 3.5%d/gm vs 1.4 +/- 0.3%d/gm, p less than 0.01), kidneys (19.1 +/- 2.1%d/gm vs 6.3 +/- 1.5%d/gm, p less than 0.001), and pancreatic tumors growing in orthotopic position (1.93 +/- 0.36%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.05). When the nude mice are pretreated with human recombinant tumor necrosis factor, localization of LAK cells compared with PBLs is even further enhanced both in tumors implanted in the pancreas (3.1 +/- 0.5%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.01) and in the subcutis (12.5 +/- 8.3%d/gm vs 0.95 +/- 0.29%d/gm, p less than 0.001).

Animals↗

Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs.

In this study, the distribution of immune spleen cells was investigated after adoptive transfer of immunity in inbred strain 2 guinea pigs. Spleen cells obtained from line 10 immune donor animals became specifically restimulated in vitro with 3 M KCl-extracted line 10 soluble proteins, but not with 3 M KCl-extracted line 1 or liver proteins. After 4 days culture in vitro, these specifically restimulated immune spleen cells retained their antitumor activity in vivo after adoptive transfer. The specifically restimulated immune spleen cells were radiolabeled with [3H]thymidine, 1 X 10(8) viable cells were adoptively transferred in tumor-bearing guinea pigs, and their distribution was investigated. As controls for the specific localization of the immune cells at the line 10 tumor, the presence of labeled cells was studied in the contralateral transplanted line 1 hepatoma as well as in cellular inflammatory reactions elicited by injection with incomplete Freund's adjuvant (IFA) and complete Freund's adjuvant (CFA). A significantly higher localization of the labeled immune spleen cells in the line 10 tumor and the first and second draining lymph nodes of the line 10 challenge site were found when compared to the influx of these cells in the line 1 tumor and the nontumor antigen-related inflammatory reactions. Because our immune donor animals were immunized with a mixture of line 10 cells and BCG, these animals are immune to both. Line 10 immune spleen cells were restimulated in vitro with PPD and were radiolabeled. These PPD-restimulated immune spleen cells showed no preferential localization at the line 10 tumor challenge site but, as expected, a tendency for localization at the CFA (H37Ra) injection site. Furthermore, PPD-reactive spleen cells from BCG-immunized guinea pigs showed a significantly higher accumulation at the CFA injection site compared to the IFA injection site and the line 10 and line 1 tumor challenge site. From the results, it is concluded that line 10 tumor-immune and BCG-immune spleen cells are two distinct cell populations, and that the existence of cross-reacting antigens between BCG and the line 10 hepatocarcinoma are of no importance for the rejection of the line 10 tumor by immune spleen cells.

Animals↗

Adoptive immunotherapy as an adjunctive treatment to thoracic irradiation for pulmonary tumor deposits in mice.

The study was performed to determine whether local thoracic irradiation (LTI) causes accumulation of adoptively transferred peritoneal exudate (PE) cells in the lung and whether such treatment improves the response of tumor deposits in the lung to LTI. Tumors in the lung were generated by sarcoma SA-NH cells injected i.v. into syngeneic (C3Hf/Kam mice. Exposure of mice to a single dose of gamma-rays ranging from 2 to 10 Gy caused a dose-dependent decrease in the number of alveolar exudate cells. Also, LTI caused a dose-dependent reduction in the number of lung tumor nodules in mice that were treated with tumor cells 4 days before irradiation. Adoptive i.v. transfer of syngeneic PE cells several hours or 2 days after LTI not only restored the radiation-depleted alveolar exudate cells to their normal levels but also led to an accumulation of transferred cells in the irradiated lung to a several-fold excess of the normal value. Maleic anhydride-divinyl ether-2-activated PE cells accumulated in the irradiated lung much more than normal PE cells and exerted antitumor activity in normal mice and in mice exposed to LTI. Their antitumor action, however, was much more pronounced in the latter, resulting in the augmentation of radioresponse of tumor nodules by a factor of 1.23. The better antitumor action of activated PE cells in mice given LTI can be ascribed to accumulation of these cells in the irradiated lung. Thus, these results show that the irradiation of the lung predisposes this tissue to accumulation of lymphoid cells, which can be beneficial in the therapy of malignant tumors by combinations of radiotherapy and adoptive immunotherapy.

Animals↗

Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors.

A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver.

Animals↗

Mechanism of action of a T suppressor factor (TsF) in contact sensitivity: the T cell target for TsF activity in adoptive transfer of immunity is not effector cell.

The passive transfer of contact sensitivity (CS) by immune cells into normal animals requires the interaction of two distinct Ly-1+ T cells, one which is Vicia villosa lectin (VV)-nonadherent, the other which adheres to VV. Functional deletion of either cell type abrogates the adoptive transfer of CS into normal animals, whereas VV-nonadherent cells alone can transfer CS into animals pretreated with cyclophosphamide (Cy). An antigen-specific T suppressor factor, designated TNP-TsF, inhibits the transfer of CS into normal adoptive recipients. TNP-TsF mediates its suppressive activity by inducing an I-J+ subfactor (designated I-J2) from the assay population by the interaction of PC1-F (a TNP-binding subfactor of TNP-TsF) with antigen-primed Ly-2+ T cells. This I-J+ subfactor then complements TNBS-F (an antigen-nonbinding subfactor of TNP-TsF) to form an antigen-nonspecific effector molecule which suppresses DTH responses in an antigen-nonspecific fashion. We report here that TNP-TsF suppresses the adoptive transfer of CS into normal animals but not into animals pretreated with Cy. TNBS-F + I-J2, the effector complex of TNP-TsF, also suppresses the transfer of CS into normal but not Cy-treated animals. When the Ly-1 immune cells were separated into VV-adherent and -nonadherent populations, the TNBS-F + I-J2 suppressor complex suppressed the functional activity of the VV-adherent cell population, but not the VV-nonadherent cells. This suppressive activity correlates with the need for VV-adherent cells in the transfer of CS into normal but not Cy-treated recipients. When an I-J+ molecule (I-J1) from an SRBC-specific TsF was used in place of I-J2 to form a suppressor complex with TNBS-F, this TNBS-F + I-J1 TsF suppressed the transfer of CS into both normal and Cy-treated recipients. This difference in functional suppressive activity correlated with a difference in target cell specificity: TNBS-F + I-J1 suppressed the VV-nonadherent TDTH cell, whereas TNBS-F + I-J2 suppressed the VV-adherent T cell of CS. Immune cells which are transferred under conditions which do not require the VV-adherent cell for transfer are not suppressed by TNBS-F + I-J2 or TNP-TsF, but are suppressed by the TNBS-F + I-J1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synergistic effects of the xid gene in X chromosome congenic mice. I. Inability of C3.CBA/N mice to respond to thymus-dependent antigens in adoptive transfer assays.

The xid gene, which causes a B lymphocyte immune defect in CBA/N mice, has been bred onto the C3H/HeN background. The resulting X chromosome congenic mice (C3.CBA/N) exhibit immunologic defects that are much more profound than the defect exhibited by CBA/N mice; thus, the B cells from C3.CBA/N mice not only fail to respond to thymus-independent (TI) type 2 antigens such as TNP-Ficoll, but they fail to respond in vitro to TI-type 1 antigens such as TNP-Brucella abortus (BA) and B cell mitogens such as LPS and Nocardia water-soluble mitogen. In this paper we show that the synergistic defect seen in C3.CBA/N B cells is also elicited in adoptive transfer assays to thymus-dependent (TD) antigens such as TNP-KLH and PC-KLH, antigens to which both parental strains respond. Thus, the secondary adoptive transfer response of C3.CBA/N spleen cells is generally less than 5% of the immune response produced by CBA/N or C3H/HeN spleen cells. This synergistic defect is restricted to the C3.CBA/N B cells, since C3.CBA/N T cells can provide help to CBA/N B cells that is equivalent to the help obtained with CBA/N T cells. The low responsiveness of C3.CBA/N spleen cells to TD antigens, which is elicited in adoptive transfer assays, is not seen when the intact animal is immunized with antigen in CFA; this, intact C3.CBA/N mice produce anti-PC-KLH and anti-TNP-KLH responses only slightly lower than the responses of CBA/N mice to these same antigens. In contrast, when these mice are immunized with phenol-extracted LPS, a TI-type 1 antigen, their antibody responses are severely depressed. These data suggest that under conditions in which T cell help may be limiting or in which the intact physiology of the T and B cells has been disrupted, C3.CBA/N B cells demonstrate profound immunologic impairment; however, when adequate T cell help is available and the splenic architecture is not disrupted, their immune responses appear to progress in a normal fashion.

Animals↗

In vivo and in vitro effect of adoptive immunotherapy of experimental murine brain tumors using lymphokine-activated killer cells.

Adoptive immunotherapy for the experimental murine brain tumor was investigated by using lymphokine-activated killer (LAK) cells both in vitro and in vivo. Supernatants of 48-h culture medium of spleen cells from Wistar rats in the presence of concanavalin A were used as interleukin 2 (IL-2). LAK cells were generated by cocultivation of spleen cells from Fischer rats with IL-2 with the peak reactivity on Day 2 or 3 of culture. Lytic activity was observed against not only syngenic tumor cells but also allogenic and xenogenic tumor cells, while no lytic activity was observed against normal brain cells. The cell depletion test, dye exclusion test, and immunofluorescence method using monoclonal antibodies revealed that LAK cells partially belonged to the population of the activated T-cell group, but the precursor cells did not react with any monoclonal antibodies used. On the basis of these results in vivo study was performed. LAK cells and immune spleen cells were adoptively transferred to the rats i.v. or intratumorally (i.t.) on the seventh day after the inoculation of T9, a gliosarcoma induced by methylcholanthrene from Fischer rats, into the right basal ganglia. Then the survival rate and necrotic foci were compared between the groups treated with those cells and the control. The survival rate of the groups treated with LAK cells was significantly higher than that of the control (administered i.v.; P less than 0.01, administered i.t.; P less than 0.05). But the treatment with immune spleen cells was not effective. The incidence and area of necrotic foci in the tumors treated with LAK cells were greater than those of the others. Microautoradiography was also performed using [3H]thymidine-labeled LAK cells, which were administered i.v. to the models on the 14th day after the inoculation of T9. It was revealed that LAK cells accumulated in the lung shortly after the administration and then in the liver and spleen, especially in the white pulp. IL-2 inhibitor activity of the sera from the tumor-bearing rats was greater than that of normal rats (P less than 0.001), but it was depressed markedly by cyclophosphamide (P less than 0.01). The adoptive transfer of LAK cells may be one of the effective treatments of malignant brain tumor. The nature of IL-2 inhibitors is necessary to be clarified for more effective immunotherapy.

Animals↗

A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-activated killer cells.

Lymphocytes from human peripheral blood incubated with interleukin-2 (IL2) develop lymphokine-activated killer (LAK) activity with the ability to kill a wide variety of tumor cells in a non-major histocompatibility complex-restricted manner. Adoptive immunotherapy with LAK cells and IL2 has been reported to lead to a regression of solid tumors in some patients with advanced malignancies. Aiming to improve the effectiveness of clinical adoptive immunotherapy, we developed a procedure for selective enrichment from human blood mononuclear cells (MNC) of IL2-activated antitumor effector cells. These cells, termed adherent LAK (A-LAK) cells because of their characteristic property of adherence to plastic, demonstrated both higher proliferative potential and greater antitumor cytotoxicity than unseparated MNC. Human A-LAK cells represented only 1 to 4% of IL2-activated MNC at 24 h but expanded from 130- to 1100-fold in 20 days. They comprised a population highly enriched in CD3-Leu19+ effector cells with antitumor activity against fresh human solid tumor cells and established cell lines. A-LAK cells retained antitumor activity for up to 14 days when cultured in the presence of IL2. They also mediated antibody-dependent cytotoxicity. Large-scale generation of A-LAK cells from the blood of patients with cancer proved feasible and should yield populations that are effective in vivo at lower doses than those required with unseparated LAK cells. This offers the potential for improving the antitumor effects, reducing the toxicity, and facilitating the administration of adoptive immunotherapy in humans. A Phase I/II clinical trial utilizing A-LAK cells and IL2 in patients with melanoma and renal cell carcinoma is now in progress.

Cell Separation↗