Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients.

Abstract

Purpose This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3-8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time to progression (TTP), and overall survival (OS). Study Design: T cells obtained by apheresis were expanded and armed with EGFRBi, cryopreserved for infusions. In a phase I dose escalation, five patients received three weekly infusions of 10-40 × 109 BATs/infusion followed by a booster infusion 3 months later, and 2 patients received 8 infusions twice weekly for 4 weeks in a phase II. The trials were registered at http://www.clinicaltrials.gov, NCT01420874 and NCT02620865. Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 109 BATs was met. The median TTP is 7 months, and the median OS is 31 months. Two patients had stable disease for 6.5 and 25+ months, and two patients developed complete responses (CRs) after restarting chemotherapy. Infusions of BATs induced anti-pancreatic cancer cytotoxicity, innate immune responses, cytokine responses (IL-12, IP-10), and shifts in CD4 and CD8 Vβ repertoire with enhanced cytoplasmic IFN-γ staining in the Vβ repertoire of the CD8 subset that suggest specific clonal TCR responses. Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival.

• Authors: Lawrence G Lum, Archana Thakur, Minsig Choi, Abhinav Deol, Vidya Kondadasula, Dana Schalk, Kristie Fields, Melissa Dufrense, Philip Philip, Gregory Dyson, Hussein D Aon, Anthony F Shields
• Journal: Oncoimmunology (Oncoimmunology) Vol. 9 Issue 1 Pg. 1773201 (06 10 2020) ISSN: 2162-4011 [Print] United States
• PMID: 32939319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Antibodies, Bispecific
• CD3 Complex
• EGFR protein, human
• ErbB Receptors

Topics

• Antibodies, Bispecific (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• CD3 Complex
• ErbB Receptors
• Humans
• Pancreatic Neoplasms (drug therapy)
• T-Lymphocytes