Targeted T-cell therapy in stage IV breast cancer: A phase i clinical trial

Lawrence G. Lum, Archana Thakur, Zaid Al-Kadhimi, Gerald A. Colvin, Francis J. Cummings, Robert D. Legare, Don S. Dizon, Nicola Kouttab, Abby Maizel, William Colaiace, Qin Liu, Ritesh Rathore

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Purpose: This study reports a phase I immunotherapy trial in 23 women with metastatic breast cancer consisting of eight infusions of anti-CD3 × anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3activated T cells (ATC) in combination with low-dose 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 IL2 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 × 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 × 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 02+ patients. Conclusions: Targeting HER2+ and HER2- tumors with aATC infusions induced antitumor responses, increases in Th1 cytokines, and IL12 serum levels that suggest that aATC infusions vaccinated patients against their own tumors. These results provide a strong rationale for conducting phase II trials.

Original languageEnglish (US)
Pages (from-to)2305-2314
Number of pages10
JournalClinical Cancer Research
Issue number10
StatePublished - May 15 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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