Spotlight on Novel Therapies to Improve Post-HCT Graft-Versus-Leukemia Effects

In the last decade, multiple novel cellular therapies have been developed to enhance graft-versus-leukemia (GVL) effects, and these advances have the potential to change the standard of care in preventing or treating post-transplant relapse. The latest research in cellular therapies, antibody-based treatments, and tyrosine kinase inhibitor (TKI)-based approaches to enhance GVL effects are outlined in articles published in a special edition of Blood.

The review articles from leaders in the field of hematopoietic cell transplantation (HCT) focus on:

  • Exploiting lymphocytes expressing the gamma delta T-cell receptor. These T cells are not alloreactive and do not induce GVHD but can exhibit potent anti-leukemia and anti-infectious activities. Drs. Rupert Handgretinger and Karin Schilbach review the clinical strategies to exploit the full function of these lymphocytes, such as the ex vivo expansion and manipulation of either patient-derived or donor-derived gamma delta T cells and their subsets.
  • Developing strategies to activate natural killer (NK) cells. Dr. Sarah Cooley and colleagues describe techniques to activate NK cells using cytokines, checkpoint modulators, and immune engagers, and then administering these in combination with novel therapeutic agents to potentially increase NK targeting of specific antigens on leukemic cells.
  • Extending the application of CAR-targeted T cells to allogeneic HCT. Adoptive transfer of autologous T cells with chimeric antigen receptors (CARs) targeting CD19 has been very successful in treating relapsed and refractory CD19-positive diseases, such as non-Hodgkin lymphoma. Although new techniques are being developed to extend CAR T cell therapy to the allogeneic setting, the risk of graft-versus-host disease (GVHD) remains. Dr. Melody Smith and colleagues review several different approaches to potentially overcome this risk.
  • Using TKIs and immune checkpoint blockades. The review by Dr. Robert Soiffer and colleagues focuses on administering tyrosine kinase inhibitors (TKIs) directed at BCR-ABL or FLT3. Current data on the two classes of checkpoint inhibitors against CTLA-4 and PD1 are discussed, both alone and in combination with donor lymphocyte infusions (DLIs) or hypomethylating agents.

Zeiser R, et al. Blood