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G L Bartlett

Publications and source records attributed to G L Bartlett.

At least 19 recordsLinked to original sources
PubMed1987

Surveillance, latency and the two levels of MCA-induced tumor immunogenicity.

Among 154 different, MCA-induced mouse sarcomas, the immunogenicities of those tumors that had had the shortest original latencies in their autochthonous hosts were of an intermediate level with relatively little scatter. This fact is not predicted by the theory of immunological surveillance, but does fit the predictions of the immunological facilitation theory of oncogenesis. The frequency distribution of the tumor immunogenicities showed 2 peaks; the cluster of higher immunogenicity had a shorter latency than did the cluster of lower immunogenicity. The data for tumors initiated within in vivo diffusion chambers also showed 2 immunogenicity clusters, suggesting that the discrete clusters were not caused by host immunity. However, immunity apparently reduced the mean latency of the more immunogenic cluster and/or lengthened the mean latency of the less immunogenic, a result also inconsistent with the theory of immunological surveillance.

Animals↗
PubMed1986

Distinct T-cell proliferative responses to 13762A rat mammary adenocarcinoma and derived clones.

We examined the in vitro responses of immune lymphocytes to the tumor antigens of the syngeneic rat mammary adenocarcinoma 13762A. This tumor readily metastasizes to lymph node and lungs and is poorly immunogenic. Rats were immunized with a highly immunogenic clone (18A) which was isolated as a spontaneous variant from the parental 13762A tumor. Clone 18A grew progressively in irradiated rats but regressed completely in normal rats. Animals immune to 18A tumor were also immune to parental 13762A. Lymphocytes obtained from the spleen and peritoneum of immune rats were tested for specific proliferation to parental 13762A tumor and clone 18A to determine whether similar cross-reactivity to these tumors occurred in vitro. We found an anatomical difference in localization of immune lymphocytes which reacted to the two tumor cell lines. Immune peritoneal exudate cells (PEC) responded strongly to clone 18A but poorly to 13762A, while immune spleen cells from the same animals responded predominantly to 13762A tumor. After 7 days culture, PEC proliferating in response to clone 18A contained 84-95% W3/25+ T-helper cells, and only 5-8% OX8+ cytotoxic/suppressor cells, while analogous cultures of spleen cells responding to parental 13762A tumor consisted of 60-80% W3/25+ cells and 20-23% OX8+ cells. Immune spleen cell cultures stimulated with 13762A tumor generated cytotoxic lymphocytes which specifically lysed both parental 13762A and clone 18A cells. We conclude that despite cross-reactivity in vivo and in vitro, antigens present on 13762A and 18A tumor cells stimulated different subsets of immune T cells.

Adenocarcinoma↗
PubMed1986

In vivo transformation of human skin with human papillomavirus type 11 from condylomata acuminata.

Human papillomaviruses (HPVs) have been implicated in the development of a number of human malignancies, but direct tests of their involvement have not been possible. We describe a system in which human skin from various sites was infected with HPV type 11 (HPV-11) extracted from vulvar condylomata and was grafted beneath the renal capsule of athymic mice. Most of the skin grafts so treated underwent morphological transformation, resulting in the development of condylomata identical to those which occur spontaneously in patients. Foreskins responded with the most vigorous proliferative response to HPV-11. The lesions produced the characteristic intranuclear group-specific antigen of papillomaviruses. Both dot blot and Southern blot analysis of DNA from the lesions revealed the presence of HPV-11 DNA in the transformed grafts. These results demonstrate the first laboratory system for the study of the interaction of human skin with an HPV. The method may be useful in understanding the mechanisms of HPV transformation and replication and is free of the ethical restraints which have impeded study. This system will allow the direct study of factors which permit neoplastic progression of HPV-induced cutaneous lesions in human tissues.

Animals↗
PubMed1986

Role of T-cell subsets in the destruction of established metastases of 13762A rat mammary adenocarcinoma.

The 13762A rat mammary adenocarcinoma metastasizes with high frequency to regional lymph nodes and lungs. The intratumoral injection of Corynebacterium parvum on day 7 followed by primary tumor excision on day 20 significantly prolonged survival and cured 10-40% of syngeneic F344 rats. Established metastases were destroyed by the treatment, and strong and specific tumor rejection immunity was induced. The purpose of the present study was to determine if T-cells were required for the C. parvum treatment to be effective and to identify the subsets of T-lymphocytes that might participate in the response. The results indicated that rats depleted by either neonatal thymectomy or a combination of adult thymectomy, 900 rad, and bone marrow reconstitution did not inhibit tumor growth after C. parvum treatment. Restoration of depleted rats with lymph node cells permitted effective treatment. The lymph node cells that were responsible for restoration expressed both W3/13 (pan-T-cell) and W3/25 (helper T-cell) membrane-associated differentiation antigens. T-cells that bore the MRC OX8 (cytotoxic-suppressor T-cell) antigen did not restore the response to C. parvum treatment. The effect of lymph node restoration was markedly potentiated by simultaneous administration of thymocytes, a T-cell population that expresses both W3/25 and MRC OX8 antigens. In conclusion, the cytotoxic-suppressor T-cells were ineffective in the restoration of T-cell-depleted, tumor-bearing rats to benefit from C. parvum but helper T-cells were highly effective, and their activity was strongly potentiated by administration of thymocyte amplifier cells.

Adenocarcinoma↗
PubMed1985

Systemic adoptive transfer of immunity and low-dose irradiation eradicate metastases of 13762A rat mammary adenocarcinoma.

Rats cured of poorly immunogenic 13762A tumor by a combination of surgery and cyclophosphamide (CY) treatments produced peritoneal exudate cells (PEC) that prevented tumor growth when transferred to naive recipients, but they were ineffective against established tumor. A highly immunogenic 13762A clone (18A) induced PEC lymphocytes that completely reversed the growth of established primary tumor and of lymph-node metastases. 18A-immune PEC alone strongly inhibited tumors of 7 days' duration, but only moderately suppressed 14-day tumors, and had no effect on 21-day tumors. Irradiation (450 R) of rats prior to tumor transplantation improved the effectiveness of the PEC given at 7 days, but the benefit had gone by 14 days. Long-term T-cell depletion prior to tumor challenge allowed PEC inhibition of 7- and 14-day tumors, but not 21-day tumors. The most potent strategy was the administration of 450 R followed immediately by immune PEC. When rats with 21-day tumors were so treated, the metastases grew temporarily to a maximum diameter of 2-5 cm and then completely regressed. We concluded that a combination of immune T cells and 450 R can cure established, massive metastases, probably through a combination of an increase in the numbers of T-cell effectors and elimination of suppressor cells.

Adenocarcinoma↗
PubMed1985

Characteristics of T cells involved in the expression of delayed hypersensitivity and tumor rejection immunity to 13762A rat mammary adenocarcinoma.

The 13762A rat mammary adenocarcinoma is poorly immunogenic and metastasizes with high frequency to regional lymph nodes and lungs. Tumor rejection immunity (TRI) may be readily transferred with oil-induced peritoneal exudate cells (PEC) from immune rats but the transfer of delayed hypersensitivity (DH) was less reliable. The purposes of the present study were: (1) to compare the optimum conditions for transfer of DH and TRI; (2) to determine whether the TRI effectors were derived from cells which recently divided in the donor; (3) to determine the relative sensitivity of DH and TRI effectors to treatment with radiation and mitomycin C; and (4) to identify the phenotypes of the T-cell subsets responsible for transfer of DH and TRI. The results indicate that transfer of DH requires more cells or a longer interval between transfer and challenge than did TRI. Treatment of the donor with vinblastine (VBL) or hydroxyurea (HU) continuously for 5 days prior to harvest of PEC impairs effectiveness of transferred DH and TRI. This indicates that the effectors proliferated during the period before harvest of the PEC. Treatment of the PEC in vitro with mitomycin C or gamma-radiation eliminates transfer of DH and TRI, but DH is more radiosensitive than TRI. T-cell subsets were identified with the monoclonal antibodies W3/13 (pan-T), W3/25 (helpers), and OX8 (cytotoxic/suppressors). The TRI effectors are nonadherent and express W3/13, W3/25, or OX8 antigens. The, DH effectors are also nonadherent but expressed only W3/13 or W3/25 antigens. Thus, DH systemic adoptive transfer requires more cells or a shorter interval between transfer and challenge than TRI. Both DH and TRI effectors replicate in the donors prior to transfer. The DH effectors are helper T cells but TRI effectors include cells with helper or cytotoxic T-cell marker antigens. We conclude that TRI and DH are probably functions of two T-cell subsets which differed in radiation sensitivity and membrane phenotype. CY pretreatment of the recipients of immune PEC potentiate TRI. The potentiated effects are reduced if the recipients are given nonadherent spleen cells. The responsible cells expressed W3/13 and W3/25 antigens. Thus, CY potentiation is attributed to the depletion of precursors of suppressor T cells.

Adenocarcinoma↗
PubMed1985

Increased immunogenicity of a spontaneous variant clone of the 13762A rat mammary adenocarcinoma.

The 13762A rat mammary adenocarcinoma is weakly immunogenic and spontaneously metastasizes to regional lymph nodes and lungs. A clone (18A) was isolated from the parental tumor, which grew for 3 weeks in normal F344 rats, forming tumors up to 2-3 cm and some nodal metastases, and then completely regressed. Pretreatment of recipient rats with 450 rad permitted progressive growth and death due to metastases. The behavior of 18A has been stable during a period of 120 days in continuous culture or for 6 in vivo passages in irradiated rats. Regression of 18A was associated with intense tumor mononuclear leukocytic infiltration, whereas parental tumors of the same size recruited few leukocytes. Regressions occurred when 18A cells were placed intradermally, sc, or im, but iv injections were not rejected. Parental tumors grew progressively at all sites. Regressor rats were specifically immune to challenge with both 18A and parental tumor but not to an unrelated mammary carcinoma (R3230AC). Irradiated 18A tumor cell vaccines protected recipients against challenge with parental tumor, but similar vaccines of irradiated parental tumor cells were ineffective. The systemic adoptive transfer of immune lymphocytes more strongly inhibited the growth of established (7 days) 18A than parental tumor. It was concluded that the parental 13762A tumor contained stable variants that were significantly more immunogenic and more susceptible to immune attack than the parental tumor. Such variant tumor lines may be useful in the study of the host response to metastasis.

Adenocarcinoma↗
PubMed1984

Relationship of tumor leucocytic infiltration to host defense mechanisms and prognosis.

The interface between the tumor and the host is often the site of leucocytic infiltration. We will examine the idea that the infiltrating leucocytes of human and experimental tumors are components of the host immunological defense against the tumor, and that the presence of the infiltrate is a marker of favorable prognosis. Leucocytes could infiltrate tumors because of an active immune response, either nonspecific or specifically directed to tumor-associated antigens. Leucocyte influx may also occur because of chemotactic factors secreted by the tumor cells. Some tumors release factors which enhance vascular permeability and permit improved access by leucocytes to the tumor focus. The consequences of leucocytic infiltration include tumor cell cytolysis, cytostasis, or stimulation of proliferation. The present state of our knowledge of the interactions between tumor cells and infiltrating leucocytes precludes broad generalization of mechanisms. Further study will probably reveal that the mechanisms are diverse, and that there are some systems in which immune interactions occur at this interface and others in which they do not.

Animals↗
PubMed1982

Corynebacterium parvum prevents immunization to admixed irradiated tumor cells by a local process.

Immunization of mice with 10(6) irradiated LSTRA murine leukemia cells (LX) induced weak immunity to subsequent tumor-cell challenge. Admixture of low doses (1.4-14 micrograms of C. parvum with the LX usually augmented the immunity. Higher doses (1,400-7,000 micrograms) of admixed C. parvum not only failed to augment immunity, but prevented immunization by the contained LX. We investigated the mechanism by which 1,400 micrograms of C. parvum mixed with 10(6) LX prevents immunization by the LX. The inhibitory effect was a function of the ratio of C. parvum to tumor cells. Injection of 1,400 micrograms C. parvum, alone or mixed with the LX, did not prevent immunization by LX given simultaneously at a separate site. Injection of C. parvum, alone or mixed with the LX, did not prevent immunization by LX injected simultaneously at a separate site sharing a common lymph-node drainage area. The high dose of C. parvum prolonged retention of radiolabelled LX at the injection site and decreased the rate of distribution of the LX to other organs, particularly the spleen. These results indicate that a high dose of C. parvum prevented immunization through a localized process at the injection site.

Adjuvants, Immunologic↗
PubMed1982

Regulation of the expression of adoptive tumor rejection immunity by recipient cyclophosphamide-sensitive cells.

Peritoneal exudate T-cells from rats immune to 13762A rat mammary tumor conferred specific tumor rejection immunity on normal recipients. The efficiency of systemic adoptive transfer of tumor rejection immunity with immune peritoneal exudate T-cells was improved by cyclophosphamide (CY) pretreatment of recipients. Optimal potentiation was obtained with a dose of 50 or 100 mg CY per kg body weight given the day before transfer. CY pretreatment of recipients was effective 1 to 3 days prior to transfer. The CY-potentiating effect was lost with longer intervals between CY administration and transfer, indicating recipient recovery. CY pretreatment enabled recipients to reject greater numbers (100 times) of tumor cells and inhibited tumor challenge established before systemic adoptive transfer. The CY-induced potentiation of systemic transfer of tumor immunity was reversed by i.v.-administered normal spleen. We concluded that CY-sensitive host regulatory cells restricted the expression of adoptive tumor rejection immunity. Control of the activity of these regulatory cells allows increased efficacy of effector T-lymphocytes in this system.

Animals↗
PubMed1981

Solubilization and partial characterization of a tumor-rejection antigen from an ultraviolet light-induced murine tumor.

Tumor rejection antigen (TRA) of an ultraviolet-light-induced murine skin tumor was solubilized, fractionated and partially characterized. Subcellular fractions were prepared by differential centrifugation of tumor cells that had been ruptured via nitrogen cavitation. Only the 110,000-g membrane fraction induced significant tumor protection, as determined by in vivo immunization and challenge assays. Extraction of the membrane fraction with 3 M KCI resulted in solubilization of material that could induce in vivo tumor-rejection immunity. Both the membrane fraction and soluble extract had a limited effective dose range. The KCI extract was separated on a Sepharose, CL-6B column in the presence of 6 M guanidine-HCI. Only one of five fraction pools (molecular weight range of 76,000-127,000 daltons) was immunogenic. It contained at least eight protein bands by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), but no lipid components. This immunogenic Sepharose fraction was chromatographed on a Sephadex G-150 column. Each of the four Sephadex fraction pools was immunogenic. One protein component was common to each of those fractions. It migrated as a single 76,000-dalton band on SDS-PAGE and contained [14C]-leucine and [3H]-glucosamine that had been incorporated during cell growth. These results suggest that the TRA of this tumor is a 76,000-dalton glycoprotein.

Animals↗
PubMed1981

Specific unresponsiveness to Corynebacterium parvum as measured by delayed hypersensitivity.

In order to induce specific unresponsiveness to C. parvum mice were given seven daily i.v./i.p. injections of a high dose of the vaccine, or were given a single dose i.v. injection of C. parvum followed by an i.p. injection of cyclophosphamide (CY). Mice given the high-dose procedure had a significant level of residual footpad reactivity to C. parvum challenge, but subsequent sensitizing injections did not stimulate delayed hypersensitivity (DH). In contrast, mice given C. parvum and CY did not respond to challenge, and they could not be sensitized to C. parvum. Their unresponsiveness was antigenically specific and was stable for at least six weeks. Antibodies to C. parvum were induced by both pretreatment procedures. This is the first report of the production of mice specifically unable to mount DH to a bacterial immune stimulant.

Animals↗
PubMed1981

Systemic adoptive transfer of immunity to 13762A rat mammary adenocarcinoma.

Rats cured of metastatic 13762A rat mammary adenocarcinoma by Corynebacterium parvum immunotherapy possess strong tumor-specific rejection immunity. Systemic adoptive transfer of lymphoreticular cells from cured rat donors conferred protective immunity on naive recipients. Fewer oil-induced peritoneal exudate cells than lymph node cells were required to transfer tumor rejection immunity. The adoptive immunity was specific since it strongly inhibited 13762A tumor growth but did not inhibit the growth of the antigenically unrelated R3230AC rat mammary tumor. Rats sensitized to the bacterial immune stimulant used to effect cure were unsuitable donors of PEC capable of transferring tumor rejection immunity. Macrophages or bone marrow-derived lymphocytes from immune donors did not transfer immunity. Treatment of peritoneal exudate with a xenogeneic antiserum specific for rat thymus-derived lymphocytes significantly reduced the efficiency of transfer. We conclude that thymus-derived lymphocytes from rats cured of 13762A tumor were required for the adoptive transfer of tumor-specific rejection immunity.

Adenocarcinoma↗
PubMed1980

Treatment of cancer using Corynebacterium parvum: similarity of two preparations in four animal tumor models.

The tumor inhibitory properties of Corynebacterium parvum obtained from Burroughs Wellcome (CP-BW) or from Institut Merieux (CP-IM) were compared in four animal tumor models: the CaD2 mouse mammary carcinoma treated by intravenous (I.V.) or intratumoral (I.T.) injection of C. parvum; 13762A rat mammary adenocarcinoma treated by I.T. injection of C. parvum either alone or combined with excision of the primary tumor; LSTRA murine leukemia and line 10 cavian hepatoma, each treated with vaccines containing irradiated tumor cells and C. parvum. Both preparations were active against each tumor. In most comparisons the potency of the two materials was not different, but in a few cases the CP-BW was effective at a lower dose than was the CP-IM. These results demonstrate the versatility of C. parvum for use in a variety of immunotherapy procedures and show that the potencies of the two major types of C. parvum are very similar.

Adenocarcinoma↗
PubMed1980

Immunotherapeutic effectiveness of BCG inactivated by various modalities.

Factors responsible for the limited effectiveness of Bacillus Calmette-Guérin (BCG) immunotherapy are completely understood. One limitation is that although the effect is dose-related, high-dose administration increases the risk of BCG toxicity, possibly the result of disseminated BCG infection. In the present study, we compared the relative effectiveness of Tice lyophilized BCG which was inactivated by heat, sonication, irradiation, streptomycin, or isoniazid (INH). The model systems were the 13762A rat mammary adenocarcinoma and the line 10 guinea pig hepatoma. In the 13762A system, tumor were injected on day 7 with living or killed BCG preparations, or with Corynebacterium parvum as a positive control. Tumors were excised on day 20. Rats treated with surgery alone usually died within 40--50 days with extensive metastases to lymph nodes, lungs, and viscera. Guinea pig line 10 hepatoma was treated with vaccine containing irradiated tumor cells and BCG. In both the rat and guinea pig models, BCG inactivated by means of irradiation was effective as viable BCG and heat-killed BCG also had a strong effect. Streptomycin treatment diminished the efficacy of the BCG and sonication destroyed BCG effectiveness even though the organisms were not all killed. The INH treatment of tumor-bearing rats did not alter the benefits of single or repeated injections of high-dose viable BCG, irradiated BCG, or C parvum. We conclude that inacativation of BCG with heat, irradiation, or INH host treatment preserves but does not improve the immunotherapeutic benefits of BCG.

Adenocarcinoma↗
PubMed1980

Augmentation of immunity of line 10 hepatoma by BCG: comparison of different BCG preparations.

The line 10 hepatoma of strain 2 guinea pigs was used in order to evaluate the adjuvant efficacy of eight Bacillus Calmette-Guérin (BCG) suspensions which differed in strain, method of preservation, or dosage. Lyophilized Tice BCG was consistently the most effective preparation. Each strain had adjuvant activity in at least one experiment. The method of preservation of BCG (fresh-frozen vs. lyophilized) did not have a consistent, a predictable influence on adjuvanticity. A ten-fold increase in the dosage of BCG or of the whole vaccine was not supraoptimal.

Adjuvants, Immunologic↗