by Dr. C.H. Weaver M.D. 1/2020
Adoptive cell transfer with autologous tumor-infiltrating lymphocytes (TILS) show promising overall response rates for the treatment of advanced cervical cancer according to results presented at the 2019 ASCO Annual Meeting. Initial data show that investigational therapy with LN-145 had a 44% overall response rate among patients with advanced cervical cancer. (1,2)
TILS are a type of adoptive cellular therapy (ACT) in which T cells are isolated based on their tumor-specific antigen recognition and then expanded outside the body and infused back into the patient.
TILs are a collection of lymphocytes that have penetrated the stroma of a cancer and are largely comprised of T cells that are actively engaged in fighting the cancer. TIL therapy requires that a biopsy be taken of the cancer from which DNA can be isolated and sequenced to identify mutations found in the cancer. TILs that can recognize the cancer are then selected, expanded, and transfused back into the patient.
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In the current study a patient’s TILs from a resected portion of their cancer were isolated and then expanded in a laboratory. The manufacturing process took 22 days. Patients then underwent lymphodepletion for 1 week with cyclophosphamide or fludarabine and were given up to six doses of interleukin-2 after the infusion of the LN-145 TILS. The entire process takes about 2 weeks from the start of lymphodepletion, followed by TIL infusion and administration ofadjuvant interleukin-2 therapy to further activate the TILS.
The current trial included 27 patients with advanced cervical cancer who received an infusion of LN-145 TILS as of May 14, 2019. Fifty-two percent of the study patients had metastatic disease, 37% had recurrent disease and 11% had persistent disease. Patients had received a median of 2.4 previous therapies that included platinum-based chemotherapy (100%), taxane - based chemotherapy (96%), VEGF inhibitors (82%), radiotherapy (74%) and PD-1/PD-L-1 inhibitors (15%).
Patients received a mean of 28 x 109 infused TIL cells that resulted in an overall response to treatment of 44% including three complete responses, nine partial responses and 11 patients with stable disease, for a disease control rate of 85.2%. Seventy-eight percent of patients showed a reduction in tumor burden. The most common side effects include chills, anemia, diarrhea, fever and low platelet counts.
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The response rate compares favorably to the 12% response rate reported for Keytruda (pembrolizumab) a recently approved immunotherapy in a similar patient population. (3) Treatment with TILS appears very encouraging, and could represent a significant advance in the overall management of metastatic cervical cancer.
- Sarnaik A, et al. Abstract 2518. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
- Jazaeri AA, et al. Abstract 2538. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
- Checkpoint Inhibitor Immunotherapy for Treatment of Advanced Cervical Cancer