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Redirecting T cells to hematological malignancies with bispecific antibodies

Mireya Paulina Velasquez, Challice L. Bonifant and Stephen Gottschalk

Abstract

There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need since it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an 'off-the-shelf' product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager (BiTE) blinatumomab has emerged as the most successful BsAb to date. It consists of two single chain variable fragments (scFvs) specific for CD19 present on B-cell malignancies, and CD3 expressed on almost all T cells. Blinatumomab has shown potent anti-tumor activity as a single agent, particularly for acute lymphoblastic leukemia (ALL) resulting in its FDA approval. However, while successful in inducing remissions, these are normally short-lived with median response durations of less than one year. Nevertheless, the success of blinatumomab has reinvigorated the BsAb field, which is bustling with preclinical and clinical studies not only for B-cell derived lymphoblastic leukemia and lymphoma, but also for acute myeloid leukemia and multiple myeloma. Here we will review successes and challenges of T-cell targeted BsAbs for the immunotherapy of hematological malignancies with special focus on conducted clinical studies and strategies to improve their efficacy.

  • Submitted June 16, 2017.
  • Accepted August 30, 2017.