Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer

OncoImmunology

Krithika Kodumudi¹  Scott M. Gilbert¹  Shari Pilon-Thomas¹  Brittany L. Bunch¹  Philippe E. Spiess¹  Wade J. Sexton¹  Autumn Joerger¹  Linda Kelley¹  Matthew Beatty¹  John Mullinax¹  Amod A Sarnaik¹  Michael Poch¹  Pasquale P. Innamarato¹  Jasreman Dhillon¹  MacLean Hall¹  Jingsong Zhang¹  Mayer N. Fishman¹  Julio M. Pow-Sang¹ 

[1] Moffitt Cancer Center and Research Institute;

关键词: t cells;    bladder cancer;    immunotherapy;    tumor-infiltrating lymphocytes;    4-1bb;   

DOI  :  10.1080/2162402X.2018.1476816

来源: DOAJ

【 摘 要 】

Advanced bladder cancer patients have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. Adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has been used successfully in treating patients with metastatic melanoma, resulting in a median OS of 52 months. In this study, we investigated the feasibility of expanding TIL from the tumors of bladder cancer patients. Primary bladder tumors and lymph node (LN) metastases were collected. Tumor specimens were minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. Expanded TIL were phenotyped by flow cytometry and anti-tumor reactivity was assessed after co-culture with autologous tumor digest and IFN-gamma ELISA. Of the 28 transitional cell bladder or LN tumors collected, 14/20 (70%) primary tumors and all of the LN metastases demonstrated TIL expansion. Expanded TIL were predominantly CD3+ (median 63%, range 10–87%) with a median of 30% CD8 + T cells (range 5–70%). TIL secreted IFN-gamma in response to autologous tumor. Addition of agonisitic 4-1BB antibody improved TIL expansion from primary bladder tumors regardless of pre-treatment with chemotherapy. This study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer.

【 授权许可】

Unknown