High-Fold Expansion of Human Cytotoxic T-Lymphocytes Specific for Autologous Melanoma Cells for Use in Immunotherapy

Jotereau, Francine; Pandolfino, Marie‐Christine; Boudart, D.; Viles, Elisabeth; Dréno, Brigitte; Douillard, Jean-Yves; Muller, Jean‐Yves; Lemevel, Bernard P.

doi:10.1097/00002371-199112000-00003

Cited by 41 publications

(31 citation statements)

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“…Improved CTL cell culture technology (12) has permitted the first clinical tests of adoptive transfer of CTLs, and the approach seems to result in substantial activity in patients with melanoma; CTLs derived from PBLs were used to treat patients with refractory, metastatic melanoma, and 8 of the 20 patients had minor, mixed, or stable antitumor immune responses (13). Furthermore, the infusion of autologous melanoma-associated antigen recognized by T cells 1-specific (MART-1-specific) CD8 + T cells into a patient with metastatic melanoma resulted in T cell infiltration into both the skin and tumor tissue (14).…”

Section: Ctl Therapymentioning

confidence: 99%

Adoptive T cell therapy for cancer in the clinic

2007

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Over the past 50 years, two fundamentally different strategies to stimulate antitumor immunity have been tested in humans: therapeutic vaccination and passive immunization. Passive immunization, herein referred to as adoptive T cell therapy, is the transfusion of autologous or allogeneic T cells into tumor-bearing hosts, i.e., patients. Evidence that T cells can help to control tumor growth has been provided by the analysis of tumor prevalence in immunodeficient mice and humans (1, 2). In the 1970s, Chester Southam and colleagues demonstrated that subcutaneous growth of human tumor autografts to patients bearing advanced cancers was inhibited by cotransfer of autologous leukocytes in about half of the patients (3). This suggested that leukocytes with a specific inhibitory effect on the implantation and growth of cancer cells were present in many patients with advanced cancer and could be used as potential candidates for adoptive immunotherapy. Furthermore, recent evidence indicates that tumor infiltration by human T cells is a powerful predictive biomarker of survival for ovarian and colorectal cancers (4, 5).Therapeutic cancer vaccines are entering the realm of clinical medicine, but despite more than 60 years of research into this therapeutic approach (6), there are currently no FDA-approved adoptive T cell therapies for cancer. However, the recent explosion of knowledge in the fields of T cell and cancer biology has enabled new approaches that might bring adoptive T cell transfer to the routine practice of clinical medicine, with an impact similar to that of the advent of transfusion medicine, which was enabled by blood bank transfusion technology in the first half of the last century. The application of recent lessons from adoptive transfer in lymphodepleted hosts (7), the ability to overcome barriers presented by Tregs (8,9), and the use of improved culture systems (10) have not yet been tested in randomized clinical trials. The intent of this review on the use adoptive T cell therapy for cancer in the clinic is to focus on issues facing the field, with an emphasis on therapy with CTLs, tumor-infiltrating lymphocytes (TILs), engineered T cells, and the use of adoptive T cell transfers to facilitate therapeutic cancer vaccines. CTL therapyAt present, there is a plethora of suitable CTL targets for many tumors (11). Improved CTL cell culture technology (12) has permitted the first clinical tests of adoptive transfer of CTLs, and the approach seems to result in substantial activity in patients with melanoma; CTLs derived from PBLs were used to treat patients with refractory, metastatic melanoma, and 8 of the 20 patients had minor, mixed, or stable antitumor immune responses (13). Furthermore, the infusion of autologous melanoma-associated antigen recognized by T cells 1-specific (MART-1-specific) CD8 + T cells into a patient with metastatic melanoma resulted in T cell infiltration into both the skin and tumor tissue (14). The in vivo efficacy of the infused T cell population was indicated by the destruction of...

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Section: Ctl Therapymentioning

confidence: 99%

Adoptive T cell therapy for cancer in the clinic

2007

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“…These populations were then expanded by a single round of stimulation with phytohemagglutinin (PHA)-L (Sigma-Aldrich) in the presence of irradiated feeder cells (allogeneic lymphocytes and B-Epstein Barr virus B cells), as described. 16 The expanded lymphocytes were transferred into 6-well tissue culture plates with fresh medium to maintain a cell density of 0.5 to 1.5 3 10 6 cell/mL.…”

Section: Isolation Of Polyclonal Cell Populations (Til Ilnl Plel Anmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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Breast cancer remains a leading cause of cancer-related death within the female population. Immunotherapy is expected to provide additional therapeutic benefits but has met so far limited success. This may be due in part to the poor understanding of immune responses to breast cancer. Although CD4 1 and CD8 1 T lymphocytes infiltrate these tumors, the phenotype and functions of these cells remain ill defined. This study was designed to investigate further about these questions, taking advantage of multiparameter flow cytometry on lymphocytes derived from peripheral blood, solid tumors, metastatic lymph nodes and pleural effusions samples of patients with breast cancer. Results showed that, in addition to conventional CD4 1 and CD8 1 ab T cells, individual tumors and most pleural effusions contained significant fractions of unconventional double positive (DP) CD4 1 CD8 1 ab T cells. These DP T cells displayed the phenotype and cytotoxic potential of effector/memory activated CD8 1 T cells but differed essentially from these cells by a high production of IL-5 and IL-13. The increased frequency of DP T cells in advanced breast cancer and their high lytic potential and original cytokine profile suggest that this T-cell subset may play a specific role in the regulation of immune responses to human breast cancer. ' 2009 UICC

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“…Melan-A-specific CTL clones were selected on the basis of their capacity to produce IL-2 in response to HLA-A*0201 Melan-A-expressing melanoma cell lines. Selected T cell clones were then expanded according to the method described previously (15).…”

Section: Generation Of Melan-a-specific Ctl Clones From Pbmcmentioning

confidence: 99%

“…One or two clones selected on the basis of their reactivity against Melan-A-expressing HLA-A2 melanoma cell lines (highest lytic activity and IL-2 secretion capacity), were expanded by a stimulation protocol previously used to grow TIL populations (15). Each patient received between 1.64 ϫ 10 8 and 2 ϫ 10 9 Melan-A-specific CTL in a single injection (Table I).…”

Section: Generation Of Melan-a-specific T Cell Clones and Injection Tmentioning

confidence: 99%

Adoptive Transfer of Tumor-Reactive Melan-A-Specific CTL Clones in Melanoma Patients Is Followed by Increased Frequencies of Additional Melan-A-Specific T Cells

Vignard

Lemercier

Lim

et al. 2005

The Journal of Immunology

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In this study, we report the adoptive transfer of highly tumor-reactive Melan-A-specific T cell clones to patients with metastatic melanoma, and the follow-up of these injected cells. These clones were generated from HLA-A*0201 patients by in vitro stimulations of total PBMC with the HLA-A*0201-binding Melan-A peptide analog ELAGIGILTV. Ten stage IV melanoma patients were treated by infusion of these CTL clones with IL-2 and IFN-α. The generated T cell clones, of effector/memory phenotype were selected on the basis of their ability to produce IL-2 in response to HLA-A*0201 Melan-A-positive melanoma lines. Infused clones were detected, by quantitative PCR, in the blood of three patients for periods ranging from 7 to 60 days. Six patients showed regression of individual metastases or disease stabilization, and one patient experienced a complete response, but no correlation was found between the detection of the infused clones in PBMC or tumor samples and clinical responses. Nonetheless, frequencies of Melan-A/A2-specific lymphocytes, measured by tetramer labeling, increased after treatment in most patients. In one of these patients, who showed a complete response, this increase corresponded to the expansion of new clonotypes of higher avidity than those detected before treatment. Together, our results suggest that infused CTL clones may have initiated an antitumor response that may have resulted in the expansion of a Melan-A-specific CTL repertoire.

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High-Fold Expansion of Human Cytotoxic T-Lymphocytes Specific for Autologous Melanoma Cells for Use in Immunotherapy

Cited by 41 publications

References 0 publications

Adoptive T cell therapy for cancer in the clinic

Adoptive T cell therapy for cancer in the clinic

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Adoptive Transfer of Tumor-Reactive Melan-A-Specific CTL Clones in Melanoma Patients Is Followed by Increased Frequencies of Additional Melan-A-Specific T Cells

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