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T cell responses in patients with melanoma resistant to multiple immunotherapies (13PD)

Date

09 Dec 2017

Session

Poster Discussion session

Presenters

Rikke Andersen

Citation

Annals of Oncology (2017) 28 (suppl_11): xi3-xi5. 10.1093/annonc/mdx710

Authors

R. Andersen1, T.H. Borch1, A. Draghi1, A. Gokuldass1, M.A.H. Rana2, M. Pedersen1, M. Nielsen1, P. Kongsted1, J.W. Kjeldsen1, M.C.W. Westergaard1, L.R. Hölmich3, H.W. Hendel4, M.S. Larsen5, Ö. Met1, I.M. Svane1, M. Donia1

Author affiliations

  • 1 Center For Cancer Immune Therapy, Department Of Haematology And Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 2 Center For Cancer Immune Therapy, Department Of Haematology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 3 Department Of Plastic Surgery, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 4 Department Of Clinical Physiology And Nuclear Medicine, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 5 Department Of Pathology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
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Background

The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing on or following treatment with CPI was able to generate functional tumor-specific immune responses.

Methods

Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions in progression on or after anti-PD-1 and anti-CTLA-4. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNa2b and IL-2 to 12 patients with CPI-resistant melanoma.

Results

TILs from 19 metastases of an equal number of patients could be assessed for T cell recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (19/19) and anti-CTLA-4 (16/19). Functional anti-tumor immune responses were detected in 15/19 patients (79%). Both CD8+ (in 14/19 patients, 74%) and CD4+ (in 14/19 patients, 74%) TILs were able to recognize autologous tumors. On average, a large fraction of CD8+ TILs (mean 25%, range 1.1-84%) recognized tumor cells. This is similar or higher than in cohorts of unselected patient populations with metastatic melanoma presented in previous studies. Additional histology analyses to identify the location of the immune infiltrates are ongoing. Out of 12 patients with anti-CTLA-4/anti-PD-1-resistant melanoma treated with TILs, two partial responses were observed, of which one is ongoing.

Conclusions

Tumor-reactive T cells appear to infiltrate heavily the tumor microenvironment of patients who failed previous CPIs. These patients can still respond to infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in anti-PD-1-/anti-CTLA-4-resistant melanoma.

Clinical trial identification

NCT02379195

Legal entity responsible for the study

Center for Cancer Immune Therapy, Herlev Hospital, Herlev, Denmark

Funding

None

Disclosure

I.M. Svane: Advisory Board and lectures: Roche, Novartis, Merck, MSD, Celgene, Incyte, TILT bio, Pfizer, BMS, Astra Zeneca; Limited grants to institution for translational research from: BMS, Roche, Novartis. M. Donia: Honorarium for lectures: MSD, BMS, Genzyme; Travel support: Novartis, MSD, BMS, Roche, Pfizer. All other authors have declared no conflicts of interest.

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