Human T Cells Specifically Activated Against Autologous Malignant Melanoma

Slingluff, Craig L.; Darrow, Timothy L.; Hf, Seigler

doi:10.1001/archsurg.1987.01400240053009

Cited by 11 publications

(3 citation statements)

References 15 publications

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“…Pooled DLN-derived cells secondarily stimulated with either tumor or PDBu plus 10 were similar in phenotype and cytotoxic activity. Similar phenotypic profiles of both TIL and DLN cells expanded in vitro have been reported [6,10,14,15,19,45]. While it is not known which subpopulation of T cells is responsible for in vivo anti-tumor activity for human cancer [7,13], cells expanded in vitro from peripheral blood, lymph nodes, or tumors have demonstrated cytotoxicity specific for autologous tumor [2,10,11,15,16,19,45,46].…”

Section: Discussionsupporting

confidence: 68%

“…Similar phenotypic profiles of both TIL and DLN cells expanded in vitro have been reported [6,10,14,15,19,45]. While it is not known which subpopulation of T cells is responsible for in vivo anti-tumor activity for human cancer [7,13], cells expanded in vitro from peripheral blood, lymph nodes, or tumors have demonstrated cytotoxicity specific for autologous tumor [2,10,11,15,16,19,45,46]. Our assessment of cytotoxic activity of cultured DLN cells against breast cancer has been limited by the availability of autologous tumor target cells.…”

Section: Discussionmentioning

confidence: 52%

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Activation and in vitro expansion of tumor‐reactive T Lymphocytes from lymph nodes draining human primary breast cancers

Sk¹,

Jl²,

McCrady³

et al. 1991

Journal of Surgical Oncology

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The feasibility of in vitro activation of lymphocytes from the draining lymph nodes (DLN) of breast cancer patients was examined. Lymphocytes isolated from 48 DLN from 12 patients were examined for their proliferative responses to rIL-2, autologous tumor cells, or rIL-2 plus tumor cells. Three general patterns of cellular responses were observed. Cells from some DLN (17%) were unresponsive to any stimuli. Lymphocytes from 52% of the DLN responded moderately to rIL-2 alone. The combination of rIL-2 and tumor antigen had a synergistic effect on the proliferation of cells from 31% of the DLN assayed. Phorbol dibutyrate and ionomycin plus rIL-2 stimulated expansion of DLN lymphocytes by up to 850-fold after 35 days. These expanded cell populations, as well as those stimulated with antigen plus rIL-2, were predominantly CD3+ and CD16- cells, varying in proportions of CD4+ and CD8+ subsets. Both populations were cytotoxic against autologous tumor, MCF-7, and K562 target cells.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 52%

Activation and in vitro expansion of tumor‐reactive T Lymphocytes from lymph nodes draining human primary breast cancers

Sk¹,

Jl²,

McCrady³

et al. 1991

Journal of Surgical Oncology

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“…This phenomenon was noted in approximately one-third of the melanomas tested, hut rarely seen with other histologies [11,18]. In one study T cells derived from patients with melanoma developed lytic specificity for autologous melanoma cells, and this specificity was enhanced by in vitro stimulation with autologous tumor [17]. Allogeneic LAK did not lyse six of our targets, therefore it is difficult to interpret the lack of autologous TIL lysis of these tumors.…”

Section: Discussionmentioning

confidence: 89%

Tumor-infiltrating lymphocytes from nonrenal urological malignancies

Haas

Solomon

Rosenberg

1990

Cancer Immunol Immunother

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Tumor-infiltrating lymphocytes (TIL) were isolated from 15 of 20 surgical specimens of transitional cell carcinoma of the urinary bladder, prostate cancer, testicular cancer, Wilms tumor and adrenal cancer. Expansion was carried out in four different culture conditions, each containing 1000 U/ml interleukin-2: RPMI medium with or without 20% (by volume) of lymphokine-activated killer cell (LAK) supernatant and AIM V medium with or without 20% LAK supernatant. The resultant cell populations were then assayed for cytotoxicity against a variety of autologous and allogeneic tumor targets and phenotypic analysis was performed with fluorescein-labeled monoclonal antibodies. TIL growth was unrelated to the initial percentage of lymphocytes or tumor cells present in the enzymatically dispersed specimens or whether fresh or cryopreserved tissue was utilized. Better growth was seen in AIM V than in RPMI medium (P = 0.013); the beneficial effect of the addition of LAK supernatant to RPMI was indicated (P = 0.065), and the addition of LAK supernatant to AIM V did not improve the ability to culture TIL (P = 0.5) from these cancers. TIL in long-term culture were predominantly CD3+. The ratio of CD4+/CD8+ cells varied with time in culture and culture medium, but most cultures eventually became CD4+. Cells bearing B cell, natural killer cell, and macrophage markers disappeared early in culture. Overall 14/15 TIL samples were lytic against one of the autologous and allogeneic targets tested, but specific lysis against the autologous tumor from which it was derived was seen in only one TIL culture originating from a bladder cancer. Our results suggest that TIL can be expanded to therapeutic levels from a variety of urological malignancies and that their potential role in future therapy should be further explored.

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Treatment of Human Melanoma Hepatic Metastases in Nude Mice With Human Cytotoxic T Lymphocytes

Crowley

Vervaert²,

Seigler³

1991

Arch Surg

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We investigated the effects of human melanoma-specific cytotoxic T lymphocytes in treating experimental human melanoma hepatic metastases in a nude mouse model of adoptive immunotherapy. Hepatic metastases were generated by intrasplenic injection of 1.5 x 10(6) human melanoma cells. Three days after injection, animals received salt solution and interleukin 2 or interleukin 2 and cytotoxic T lymphocytes. Twenty-four of 25 control animals had developed multiple tumor nodules in the liver; 11 of 13 animals receiving only interleukin 2 also had significant tumor burdens. In striking contrast, 17 of 18 animals receiving cytotoxic T lymphocytes and interleukin 2 had no gross or histologic evidence of tumors. The remaining animal had a 2-mm nodule. Human tumor-specific cytotoxic T lymphocytes are effective in vivo in a model of adoptive immunotherapy and may prove useful in adoptive immunotherapy of humans with metastatic melanoma.

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Human T Cells Specifically Activated Against Autologous Malignant Melanoma

Cited by 11 publications

References 15 publications

Activation and in vitro expansion of tumor‐reactive T Lymphocytes from lymph nodes draining human primary breast cancers

Activation and in vitro expansion of tumor‐reactive T Lymphocytes from lymph nodes draining human primary breast cancers

Tumor-infiltrating lymphocytes from nonrenal urological malignancies

Treatment of Human Melanoma Hepatic Metastases in Nude Mice With Human Cytotoxic T Lymphocytes

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