Abstract 3595: A retrospective analysis of the clinical characteristics of metastastic solid cancer patients with cytokine-induced killer cells combined immune checkpoint inhibitor immunotherapy
Authors: Choi Jonggwon , Kim Jong Yeup , Yang Dong Won , Nam Gun He 
Published: March 2024

Background: Cytokine-induced killer cells (CIKs), obtained through ex vivo expasion from peripheral blood mononuclear cells, are phenotypically and functionally shared with both T and NK cells. Within the T cell group, it can be classified into a group that simultaneously expresses CD3 and CD56 molecules (range: 30% to 70%) and a group representing CD3+ CD56- phenotype (range: 20% to 60%). It also contains a small population (&lt; 30%) of CD3 CD56+ NK cells. They can exhibit potent MHC-unrestricted cytotoxicity for both hematologic and solid tumors, but they are not harmful in hematopoietic precursors and normal tissues. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. PD-1 blockade antibody might significantly increase the cytotoxic potency of CIK cells via increasing proliferative capacity and IFN-r secretion. This retrospective study is the first to combine CIK cells with PD-1/PD-L1/CTLA-4 blockade(Immune checkpoint inhibitors, ICIs) in patients with metastatic solid cancers.

Methods: We analyzed 225 heavily treated metastastic solid cancer patients receiving CIK cell (Immunecell-LC, GC cell inc provide.) and with ICIs. Blood Sampling for CIK cells production was performed after 3 days after ICIs administration. Patients received a single intravenous infusion of activated autologous CIK cells every 2 weeks. ICIs was administered according to the protocol of each drug regardless of the CIK cells administration date. The primary end points were safety and adverse event (AE) profiles. Objective responses, overall survival (OS), progression-free survival (PFS), and diseae control rate were secondary end points.

Results: Treatment-related AEs occurred in 154/225 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in 28 patients. All treatment-related AEs were tolerable and no death due to autoimmune disease. When administration ICIs, CIK cells exhibited excellent antitumor properties and increased IFN-γ secretion. Objective responses (complete or partial responses) were observed in 67 of the 225 patients. One patients with hepatocellular carcionma had complete response. In most patients who showed an objective response, the effectiveness was maintained for more than 6 months. The overall disease control rate in the patients was 58.9%. At the time of this report, the median OS and PFS were 18.6 and 7.1 months in hepatocellular carcinoma patients and were 13.1 and 6.5 months in triple negative breast cancer patients, respectively.

Conclusion: Treatment with activated autologous CIK cells and ICIs was safe and exerted encouraging antitumor activity in metastastic solid cancers. Phase 2 clinical studies for each tumor type will be conducted.

Keywords: Cytokine-induced killer cells, Immune check inhibitors, Safety, Objective response

Citation Format: Jonggwon Choi, Jong Yeup Kim, Dong Won Yang, Gun He Nam. A retrospective analysis of the clinical characteristics of metastastic solid cancer patients with cytokine-induced killer cells combined immune checkpoint inhibitor immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3595.