Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T Cell Transfer Immunotherapy

By S. Rosenberg, Jie Yang, R. Sherry, U. Kammula, M. Hughes, G. Phan, D. Citrin, N. Restifo, P. Robbins, J. Wunderlich and 5 more. Clinical Cancer Research, 2011

1,972 citations recorded by the source corpus.

Purpose: Most treatments for patients with metastatic melanoma have a low rate of complete regression and thus overall survival in these patients is poor. We investigated the ability of adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate durable complete regressions in heavily pretreated patients with metastatic melanoma. Experimental Design: Ninety-three patients with measurable metastatic melanoma were treated with the adoptive transfer of autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen on three sequential clinical trials. Ninety-five percent of these patients had progressive disease following a prior systemic treatment. Median potential follow-up was 62 months. Results: Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) in the 3 trials using lymphodepleting preparative regimens (chemotherapy alone or with 2 or 12 Gy irradiation) were 49%, 52%, and 72%, respectively. Twenty of the 93 patients (22%) achieved a complete tumor regression, and 19 have ongoing complete regressions beyond 3 years. The actuarial 3- and 5-year survival rates for the entire group were 36% and 29%, respectively, but for the 20 complete responders were 100% and 93%. The likelihood of achieving a complete response was similar regardless of prior therapy. Factors associated with objective response included longer telomeres of the infused cells, the number of CD8+CD27+ cells infused, and the persistence of the infused cells in the circulation at 1 month (all P2 < 0.001). Conclusions: Cell transfer therapy with autologous TILs can mediate durable complete responses in patients with metastatic melanoma and has similar efficacy irrespective of prior treatment. Clin Cancer Res; 17(13); 4550–7. ©2011 AACR.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/426b5010bf6ca73ca5f34522c92177e8a719a3fd

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In Immunology

1. S. Rosenberg
2. N. Restifo
3. M. Dudley
4. Jie Yang
5. R. Sherry
6. U. Kammula
7. M. Hughes
8. J. Wunderlich

In Oncology

1. S. Rosenberg
2. N. Restifo
3. M. Dudley
4. Jie Yang
5. R. Sherry
6. U. Kammula
7. M. Hughes
8. J. Wunderlich

Citations in the corpus

• PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors. (2014, background): “The latter appear to be of critical importance for the antitumor responses observed after transfer of TILs, given the substantial regression of metastatic melanoma in up to 72% of patients in phase 2 clinical trials, in the absence of any autoimmune side effects in the great majority of patients (2)”
• IL-2: The First Effective Immunotherapy for Human Cancer (2014, background): “In contrast, TILs mediated complete tumor rejection in the absence of melanocyte toxicity in most patients, suggesting that these shared melanocyte Ags were not the tumor rejection Ags (66).”
• A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations (2018, background): “Immunotherapies that stimulate the immune system to attack tumors, including immune checkpoint blockade and adoptive T cell therapies, have achieved spectacular results in tumor types with high mutational burden, such as melanoma (36).”