Journal
BLOOD
Volume 139, Issue 17, Pages 2706-2711Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2021014648
Keywords
-
Categories
Funding
- Leukemia and Lymphoma Society Specialized Center of Research (SCOR) awards [7001-14]
- Cookies for Cancer Research grant
- Cancer Prevention and Research Institute of Texas (CPRIT) Texas Access to Cancer Cell Therapies (TACCT) grant [RP180785]
- CPRIT Early Career Clinical Investigator Award [RP200584]
- Edward P. Evans Foundation Discovery Research Grant
- Dan L. Duncan Com-prehensive Cancer Center from the National Institutes of Health (NIH) , National Cancer Institute [P30CA125123]
Ask authors/readers for more resources
Infusion of donor-derived multiple leukemia antigen-specific T cells may prevent disease relapse in patients with acute lymphoblastic leukemia (ALL) by targeting leukemia cells and minimizing the risk of graft-versus-host disease.
Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 x 10(7) to 2 x 10(7) cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no dose-limiting toxicity, acute GVHD or cytokine release syndrome. Six of 8 evaluable patients remained in long-term complete remission (median: 46.5 months; range, 9-51). In these individuals we detected an increased frequency of tumor-reactive T cells shortly after infusion, with activity against both targeted and nontargeted, known tumor-associated antigens, indicative of in vivo antigen spreading. By contrast, this in vivo amplification was absent in the 2 patients who experienced relapse. In summary, infusion of donor-derived mLSTs after allogeneic HSCT is feasible and safe and may contribute to disease control, as evidenced by in vivo tumor-directed T-cell expansion. Thus, this approach represents a promising strategy for preventing relapse in patients with ALL.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available