Targeted T cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial
Menée sur 23 patientes atteintes d'un cancer métastatique du sein, cet essai de phase I évalue l'activité antitumorale d'une immunothérapie à base de lymphocytes T armés par un anticorps bispécifique anti-CD3 et anti-HER2
PURPOSE: This study reports a phase I immunotherapy (IT) trial in 23 women with metastatic breast cancer consisting of eight infusions of anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3 activated T cells (ATC) in combination with low dose interleukin 2 (IL-2) and granulocyte-macrophage-colony stimulating factor to determine safety, maximum tolerated dose (MTD), technical feasibility, T cell trafficking, immune responses, time to progression, and overall survival (OS). EXPERIMENTAL DESIGN: ATC were expanded from leukapheresis product using IL-2 and anti-CD3 monoclonal antibody and armed with HER2Bi. In 3+3 dose escalation design, groups of 3 patients received 5, 10, 20, or 40 x 109 armed ATC (aATC) per infusion. RESULTS: There were no dose limiting toxicities and the MTD was not defined. It was technically feasible to grow 160 x 109 ATC from a single leukapheresis. aATC persisted in the blood for weeks and trafficked to tumors. Infusions of aATC induced anti-breast cancer responses and increases in immunokines. At 14.5 weeks after enrollment, 13 of 22 (59.1%) evaluable patients had stable disease and 9 of 22 (40.9%) had progressive disease. The median OS was 36.2 months for all patients, 57.4 months for HER2 3+ patients, and 27.4 months for HER2 0-2+ patients. CONCLUSIONS: Targeting HER2 positive and negative tumors with aATC infusions induced anti-tumor responses, increases in Th1 cytokines and IL-12 serum levels that suggest that aATC infusions vaccinated patients against their own tumors. These results provide a strong rationale for conducting phase II trials.