Abstract

This year we reported CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-CAR in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Our results also highlight the critical role played by antigen density in regulating CAR function. In addition, with Peter Aplan, we showed myeloablative hematopoietic stem cell transplantation improves survival but is not curative in a pre-clinical model of myelodysplastic syndrome. The work on this project concluded in February 2018.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011295-09
Application #
9779848
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Shalabi, Haneen; Wolters, Pamela L; Martin, Staci et al. (2018) Systematic Evaluation of Neurotoxicity in Children and Young Adults Undergoing CD22 Chimeric Antigen Receptor T-Cell Therapy. J Immunother 41:350-358
Fry, Terry J; Shah, Nirali N; Orentas, Rimas J et al. (2018) CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 24:20-28
Shalabi, Haneen; Kraft, Ira L; Wang, Hao-Wei et al. (2018) Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica 103:e215-e218
Jacobsohn, David A; Loken, Michael R; Fei, Mingwei et al. (2018) Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression. Biol Blood Marrow Transplant 24:2040-2046
Shah, Nirali N; Watson, Theresa M; Yates, Bonnie et al. (2017) Procalcitonin and cytokine profiles in engraftment syndrome in pediatric stem cell transplantation. Pediatr Blood Cancer 64:
Walker, Alec J; Majzner, Robbie G; Zhang, Ling et al. (2017) Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase. Mol Ther :
Allen, Elizabeth S; Stroncek, David F; Ren, Jiaqiang et al. (2017) Autologous lymphapheresis for the production of chimeric antigen receptor T cells. Transfusion 57:1133-1141
Shah, Nirali N; Fry, Terry J (2017) Anti-CD19 resistance can ""stem"" from progenitors. Blood 130:1961-1963
Gough, Sheryl M; Goldberg, Liat; Pineda, Marbin et al. (2017) Progenitor B-1 B-cell acute lymphoblastic leukemia is associated with collaborative mutations in 3 critical pathways. Blood Adv 1:1749-1759
Stroncek, David F; Lee, Daniel W; Ren, Jiaqiang et al. (2017) Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells. J Transl Med 15:59

Showing the most recent 10 out of 28 publications