Therapeutic Advances in Medical Oncology (Jul 2022)

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer

  • Valentina Hoyos,
  • Spyridoula Vasileiou,
  • Manik Kuvalekar,
  • Ayumi Watanabe,
  • Ifigeneia Tzannou,
  • Yovana Velazquez,
  • Matthew French-Kim,
  • Wingchi Leung,
  • Suhasini Lulla,
  • Catherine Robertson,
  • Claudette Foreman,
  • Tao Wang,
  • Shaun Bulsara,
  • Natalia Lapteva,
  • Bambi Grilley,
  • Matthew Ellis,
  • Charles Kent Osborne,
  • Angela Coscio,
  • Julie Nangia,
  • Helen E. Heslop,
  • Cliona M. Rooney,
  • Juan F. Vera,
  • Premal Lulla,
  • Mothaffar Rimawi,
  • Ann M. Leen

DOI
https://doi.org/10.1177/17588359221107113
Journal volume & issue
Vol. 14

Abstract

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Purpose: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. Materials and methods: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 10 7 /m 2 . Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. Results: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. Conclusion: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC.