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PubMed1986

An adoption study of genetic and environmental factors in drug abuse.

In a sample of 242 male and 201 female adoptees who had been separated at birth from biologic parents, adult adoptee diagnoses of alcohol abuse, drug abuse and antisocial personality were correlated with biologic and environmental factors. Three etiologic relationships with drug abuse were found: drug abuse was highly correlated with antisocial personality, which in turn was predicted from antisocial biologic background; a biologic background of alcohol problems predicted increased drug abuse in adoptees who did not have antisocial personalities; and environmental factors of divorce and psychiatric disturbance in the adoptive family were associated with increased drug abuse.

Adoption↗
PubMed1994

Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark.

BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.

Adolescent↗
PubMed1991

Suppressive effects of visceral tumor on the generation of antitumor T cells for adoptive immunotherapy.

Antitumor reactive cells can be generated from lymphoid organs of mice bearing subcutaneous (SC), but not liver or lung, tumors by in vitro sensitization with irradiated tumor and interleukin 2. To examine whether visceral tumors mediated tumor-induced suppression, in vitro sensitization cells were generated from mice bearing SC tumors with and without concomitant liver or lung tumors. Antitumor efficacy of these cells was assessed in adoptive immunotherapy experiments. The presence of visceral tumors suppressed the ability to generate therapeutic in vitro sensitization cells from mice with SC tumors. By establishing visceral tumors at different intervals in relationship to SC tumor inoculation, we found that visceral tumor appeared to suppress directly the development of a host immune response to SC tumor, rather than inhibit function of established immune cells. Our model affords a means to study mechanisms of tumor-induced immunosuppression.

Animals↗
PubMed1996

A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma.

BACKGROUND: A previous pilot study from our group suggested that: (1) adoptive immunotherapy (A1) with tumor-infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) may be applied with safety to more than 80% of the patients who had surgery for Stage III nonsmall cell lung carcinoma (NSCLC); and (2) AI could be useful in patients with locally advanced disease. The present randomized study was planned to assess the efficacy of AI in the postoperative treatment of Stage II, IIIa, or IIIb NSCLC: METHODS: TIL were expanded in vitro from tissue samples obtained from the surgically removed specimens of 131 patients. Eighteen cultures yielded no growth of TIL. The remaining 113 patients were stratified according to disease stage and randomized to receive AI or standard chemoradiotherapy. TIL were infused intravenously 6 to 8 weeks after surgery, rIL-2 was administered subcutaneously at escalating doses for 2 weeks, and then at reduced doses for 2 weeks and then for 2 to 3 months. RESULTS: Three-year survival was significantly better (P < 0.05) for patients who underwent AI than for controls. AI was of no benefit to patients with Stage II NSCLC, potentially useful to patients with Stage IIIa NSCLC (P = 0.06), and significantly advantageous to patients with Stage IIIb (T4) NSCLC (P < 0.01). For patients with Stage III NSCLC, local relapse (but not distant relapse) was significantly reduced following AI (P < 0.05). CONCLUSIONS: AI should be considered when designing future adjuvant therapy protocols for the treatment of NSCLC:

Antineoplastic Agents↗
PubMed1994

Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response.

BACKGROUND: The adoptive transfer of interleukin-2 (IL-2)-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. METHODS: Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. RESULTS: Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In-labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = < 0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P2 = 0.022). CONCLUSIONS. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.

Adolescent↗
PubMed2000

Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors.

In vitro, tumor-selective Hsp70 plasma membrane localization correlates with increased sensitivity to lysis mediated by a subpopulation of human natural killer (NK) cells that adhere to plastic following cytokine stimulation. In the present study, we analyzed the capacity of adoptively transferred human NK cells in SCID/beige mice for local tumor control and prevention of metastatic dissemination of Hsp70-expressing CX(+) and non-expressing CX(-) tumors following orthotopic (o.t.) injection. Both tumor sublines were derived by cell sorting of the original cell line, CX2, and thus exhibit an identical MHC and adhesion molecule expression pattern but differ with respect to Hsp70 plasma membrane expression. Viability of adherent, human NK cells in SCID/beige mice up to 18 days and the capacity to migrate have been demonstrated. Growth of Hsp70-expressing and non-expressing CX(+) and CX(-) tumor cells was completely suppressed when 10 x 10(6) NK cells were injected into the i.p. cavity on day 4 after inoculation of 2.5 x 10(6) tumor cells. Although a single injection of 5 or 2.5 x 10(6) NK cells was not sufficient to suppress tumor growth completely in all mice, the reduction in size of CX(+) tumors was significantly greater than that of CX(-) tumors. To mimic the clinical situation, ex vivo stimulated NK cells were injected i.v. on day 4 after o.t. injection of tumor cells. Under these conditions, growth of Hsp70-expressing primary tumors and metastases was suppressed. If CX(-) tumor cells were injected, 3 of 9 mice developed Hsp70-negative primary tumors. However, none of these mice developed distant metastases. In summary, our data indicate that Hsp70 acts as a recognition structure for adherent NK cells in a SCID/beige mouse model.

Animals↗
PubMed1994

Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy.

Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy.

Antigens, Viral↗
PubMed2003

Professional opportunities and responsibilities in the provision of genetic information to children relinquished for adoption.

We report a case involving the disclosure of BRCA1 mutation results to a woman who had placed a child for adoption 30 years prior to learning her mutation status. The disclosure of the mother's genetic test result to the son resulted in unexpected subsequent communications. This article briefly describes the experience and discusses the unique issues that arise in counseling a parent who has relinquished a child who is subsequently at risk to inherit a mutation for an adult onset genetic condition.

Adolescent↗
PubMed2005

Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells.

OBJECTIVE: Regulatory T cells play an important role in the prevention of autoimmunity and have been shown to be effective in the treatment of experimental colitis, a T cell-mediated and organ-specific disease. We previously demonstrated that intrinsic CD25+ regulatory T cells modulate the severity of collagen-induced arthritis (CIA), which, in contrast to colitis, is a systemic antibody-mediated disease and an accepted model of rheumatoid arthritis. We undertook this study to determine whether regulatory T cells have the potential to be used therapeutically in arthritis. METHODS: We transferred CD4+,CD25+ T cells into mice exhibiting arthritis symptoms, both immunocompetent mice and mice subjected to lethal irradiation and rescued with syngeneic bone marrow transplantation. RESULTS: A single transfer of regulatory T cells markedly slowed disease progression, which could not be attributed to losses of systemic type II collagen-specific T and B cell responses, since these remained unchanged after adoptive transfer. However, regulatory T cells could be found in the inflamed synovium soon after transfer, indicating that regulation may occur locally in the joint. CONCLUSION: Our data indicate that CD25+ regulatory T cells can be used for the treatment of systemic, antibody-mediated autoimmune diseases, such as CIA.

Adoptive Transfer↗
PubMed1996

The fate of adoptively transferred antigen-specific T cells in vivo.

In this study, anti-major histocompatibility complex class I Ld T cell receptor (TCR)-transgenic cells were adoptively transferred into severe-combined immunodeficient (Scid) mice which express the Ld Ag on all nucleated cells, and the fate of transferred antigen-specific T cells (ASTC) was followed in vivo. It was found that, after encountering antigen (Ag) in vivo, the number of ASTC increased 10-15-fold followed by a decline in number to a value that was still above the starting value. The expansion of ASTC could be abrogated by blocking CD28 on the T cells prior to Ag stimulation. Using the technique which simultaneously stains ASTC surface markers and apoptotic cells, we have not only demonstrated directly that the ASTC that disappeared from the periphery died by activation-induced apoptosis but also studied their kinetics in vivo. The remaining ASTC moderately down-regulated both TCR and CD8 on their cell surface and were fully unresponsive when cultured with Ld+ cells even in the presence of exogenous interleukin (IL)-2 and IL-4. However, they were still susceptible to apoptosis when transferred into a secondary host that provided a new source of Ag and antigen-presenting cells. These studies indicate that peripheral T cell tolerance can be induced by multiple mechanisms in which activation-induced ASTC apoptosis plays an important role.

Animals↗
PubMed1996

CD4+CD8- thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer.

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

Adoptive Transfer↗
PubMed2003

Tumor-localization by adoptively transferred, interleukin-2-activated NK cells leads to destruction of well-established lung metastases.

We have shown previously that i.v. injection of interleukin-2-(IL-2) activated natural killer (A-NK) cells together with IL-2 leads to a substantial localization of the A-NK cells into most, but not all, well-established B16 lung metastases in C57BL/6 mice within 12-24 hr. We demonstrate that the morphology of the lung metastases, (loose or more compact in appearance), and their location in the lungs (on the surface or deep in the lung parenchyma) are closely tied to the infiltration-permissiveness of the metastases as well as their sensitivity to treatment with A-NK cells. Although more than 1100 A-NK cells/mm(2) were found in deep metastases with a "loose" morphology (D-L), only 534, 90 and 89 cells/mm(2) were found in surface-loose (S-L), surface-compact (S-C) and deep-compact (D-C) metastases, respectively. The best infiltrated metastases responded best to the A-NK cell therapy. Thus, metastases of the D-L phenotype became reduced by 65-90% after treatment with 2 x 10(6) A-NK cells and IL-2 (120000 IU Peg-IL-2 every 12 hr for 3 days) compared to similar lesions in animals treated with PEG-IL-2 alone. In contrast, poorly infiltrated metastases, that is lesions of the compact phenotype (D-C and S-C) as well as loose metastases on the lung surface (S-L), did not react significantly to this treatment. We conclude that adoptively transferred A-NK cells are able to eliminate even well-established metastases. The existence of metastases that are resistant to infiltration by the transferred effector cells at time of treatment might reduce the efficacy of cell-based immuno-therapeutic ventures.

Adoptive Transfer↗
PubMed2005

Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer.

The majority of cervical cancers are caused by human papillomavirus type 16 (HPV16). Cervical cancer is associated with an ineffective host immune response against the HPV16 oncoproteins, characterized by the lack of the strong E6-specific T-helper type 1 (Th1) immunity that is generally present in healthy individuals, the presence of improperly polarized HPV16E6- and E7-specific CD4(+) T cells and increased numbers of regulatory T cells. Therefore, immunotherapeutic intervention is likely to require a modality that deletes the regulatory T cell component and enhances the HPV16-specific Type 1 T cell response. HLA-matched allogeneic stem cell transplantation may offer such a modality, because it involves the eradication of host immune cells and enables the transfer of donor derived tumor-specific T cells to the patient. As a first step in the development of such a treatment, we evaluated the success rate of a protocol for enrichment of HPV16E6-specific CD4(+) T cells from healthy donor PBMC on the basis of their IFNgamma secretion. After a short in vitro stimulation with overlapping 30 amino acid long HPV16E6 peptides, we enriched the IFNgamma secreting cells by magnetic cell sorting. The obtained polyclonal CD4(+) T cell populations recognized distinct epitopes within HPV16E6, as well as E6 protein, processed and presented by autologous professional antigen presenting cells. The described protocol proved successful in PBMC from more than half of the healthy adult blood donors. These HPV16E6-specific CD4(+) T cells may turn out to be an essential component of future adoptive T cell therapy for advanced cervical cancer, by orchestrating CTL dependent and independent tumoricidal mechanisms.

CD4-Positive T-Lymphocytes↗
PubMed1992

Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy.

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Some approaches to improve the therapeutic effectiveness of adoptive chemoimmunotherapy with spleen cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor.

Spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose L-PAM therapy (L-PAM TuB spleen cells) were previously shown to be capable of bringing about the complete regression of a large (15 to 20 mm) s.c. MOPC-315 tumor in a substantial percentage of T-cell-deficient (athymic nude) mice that had been treated with low-dose L-PAM (adoptive chemo-immunotherapy; ACIT). Here we show that aggressive depletion of CD4+T-cells by treatment both of spleen-cell donors and of recipients with anti-L3T4 monoclonal antibody (MAb) greatly improved the therapeutic effectiveness of L-PAM TuB spleen cells in ACIT. In the light of the apparent importance of cytotoxic T-lymphocytes (CTLs) for tumor eradication in low-dose L-PAM-treated MOPC-315-tumor bearers, it is interesting that treatment of L-PAM TuB spleen-cell donors with anti-L3T4 MAb was found to result in the generation of enhanced splenic anti-MOPC-315 cytotoxicity. Although most athymic nude mice in which the tumor had apparently completely regressed following ACIT remained tumor-free, approximately 1/3 of the mice relapsed. However, a substantial percentage of the relapsing mice were rescued by a low dose of L-PAM, which was not effective in causing tumor regression in athymic nude mice bearing a comparably large tumor if the mice had not been subjected previously to ACIT. Almost all athymic nude mice that had been "cured" of a large MOPC-315 tumor by ACIT but did not resist a subsequent MOPC-315 tumor challenge were rescued by low dose L-PAM. Thus, the therapeutic effectiveness of L-PAM TuB spleen cells in ACIT may be improved by aggressive depletion of CD4+ T-cells, suggesting that a low dose of L-PAM, which leads to the acquisition of potent splenic-tumor-eradicating immunity in BALB/c mice bearing a large MOPC-315 tumor, does not eliminate completely (or possibly not at all) the inhibitory activity of CD4+ T-cells. In addition, athymic nude mice that are not endowed with fully protective tumor-eradicating immunity following ACIT still have a substantial residual anti-tumor immune potential that can be exploited to bring about eradication of a large tumor burden following low-dose L-PAM therapy.

Animals↗
PubMed1994

Qualitative and quantitative intratumoral changes in gene expression following cyclophosphamide injection and the adoptive transfer of T cells: the potential contribution of tumor-associated macrophages.

Adoptive immunotherapy (AIT) of mice bearing the MCA/76-9 rhabdomyosarcoma in combination with cyclophosphamide (CY) injection results in the permanent regression of tumors. This report is concerned with changes in the tumor-associated macrophage (TAM) population and the influence of both CY injection and CY/AIT on their potential functions. Sequential analyses of FcR, MAC-I and Class-II MHC antigen expressed by tumor-associated cells (TAC) showed that CY injection or CY/AIT induced marked increases in the proportions of all 3 parameters as compared with the relatively stable levels in progressing tumors. These changes were time- and treatment-related. The mean MAC-I fluorescence (antigen density per cell) increased nearly 2-fold by 48 hr after CY injection, regardless of subsequent AIT. In contrast, the density of Class-II antigen per cell declined by as much as 75% within 48 hr after CY injection and did not recover by 7 days. This initial decline was also seen after CY/AIT and was followed by a rapid recovery to near-normal values by day 7. Northern analysis of RNA isolated from whole tumor tissue indicated wide fluctuations in expression of the typical macrophage genes encoding the proteins MAC-I, IL-I alpha, IL-I beta, TNF alpha, IA beta and c-fms. However, with the exception of MAC-I and IL-1 alpha/IL-1 beta mRNA, the modifications appeared to be qualitative rather than representing changes in the proportions of TAM. The data suggest that the changes in membrane antigen and gene expression by TAM reflect a complex interaction between TAM and their environment, in particular tumor cells and tumor-infiltrating lymphocytes. In addition, it is evident that CY injection per se is responsible for defined fundamental changes that presumably influence the outcome of AIT.

Animals↗
PubMed1994

Adoptive immunotherapy of established tumors. Acquisition of radioresistance by tumor-specific T cells after passive transfer into tumor-bearing recipients.

The present study was undertaken to determine the sensitivity to ionizing irradiation of T cells from mice immunized against the Meth-A fibrosarcoma and P815 mastocytoma after the transfer of these cells into tumor-bearing recipients. It was found that T cells from memory-immune donors were destroyed by exposing recipients to 500 rad of gamma irradiation up to 48 hr after transfer of the cells, but not thereafter. In contrast, activated immune cells were resistant to irradiation immediately after transfer. T cells were considered to be actively immune if they were harvested from donors in the process of rejecting their tumor, and were replicating, as evidenced by sensitivity to vinblastine. Memory-immune cells, on the other hand, were T cells that were harvested long after rejection of the immunizing tumor and were vinblastine-resistant. Additional results showed that CD8+ memory T cells were needed to cause regression of Meth-A tumor in recipients, whereas CD4+ memory T cells were needed for P815 tumor regression. These results support the idea that T cells that mediate tumor regression in this model of adoptive immunotherapy are radiosensitive while resting, and radioresistant after becoming activated. This knowledge needs to be taken into account when considering ionizing radiation as an immunomodulating agent for tumor immunotherapy.

Animals↗
PubMed2003

Adoptive transfer of an anti-MART-1(27-35)-specific CD8+ T cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID mice.

The identification of appropriate mouse models could be useful in carefully evaluating the actual role of the in vivo development of antigen-loss variants during antigen-specific vaccine therapy of human tumors. In this study we investigated the level of efficacy of a MART-1/Melan-A-specific CD8+ T cell clone against its autologous melanoma in a severe combined immunodeficiency (SCID) mouse model, in which the tumor cells expressed in vivo heterogeneous and suboptimal levels of MART-1. The subcutaneous co-injection of the MART-1/Melan-A-reactive T cell clone A42 with MART-1/Melan-A+ autologous human melanoma cells into SCID mice caused a total inhibition of tumor growth. However, the systemic treatment with A42 clone lymphocytes resulted in only 50-60% inhibition of tumor growth, although the T cell clone targeted the tumors and the MART-1+ cells virtually disappeared from the tumors. This study suggests that an immunotherapy based on the expansion of an antigen-specific T cell clone generated in vitro is highly efficient in abolishing tumor growth when the target antigen is fully expressed, but leads to in vivo immunoselection of antigen-loss variants in the presence of suboptimal levels of antigen expression. Furthermore, this work shows that human tumors/SCID mouse models may be useful in evaluating the in vivo efficacy of adoptive immunotherapies.

Animals↗