My research focuses on preclinical development, bench-to-bedside translation, and clinical evaluation of novel cellular immunotherapeutic approaches, with an expertise in chimeric antigen receptor (CAR-)T cell therapy.
A CAR is comprised of an extracellular antigen recognition domain linked to intracellular T cell signaling domains, which after introduction into the T cell enables T cell activation upon encounter with the target antigen. Clinical trials of CAR-T cells targeting CD19 have demonstrated impressive results in the treatment of patients with relapsed/refractory B-cell malignancies such acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia (CLL), with response rate >80% for some cancers, highlighting the promise and feasibility of this cellular therapeutic approach.
My laboratory aims to: (a) develop CAR-T cells targeting other malignancies, such as myeloma, and (b) modify CAR-T cells so as to improve efficacy and decrease toxicity. We are exploring multi-antigen targeting approaches, modifications to the CAR construct, and different approaches to T cell manufacturing.
My clinical research with the Leukemia/BMT Program of BC focuses on the development of a CAR-T program in BC and involvement in clinical trials of CAR-T cell therapy.
Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, Li D, Cherian S, Chen X, Pender BS, Hawkins RM, Vakil A, Steinmetz RN, Acharya UH, Cassaday RD, Chapuis AG, Dhawale TM, Hendrie PC, Kiem H-P, Lynch RC, Ramos J, Shadman M, Till BG, Riddell SR, Maloney DG & Turtle CJ. The response to lymphodepletion impacts PFS in aggressive non-Hodgkin lymphoma patients treated with CD19 CAR-T cells. Blood blood-2018-2011-887067, 2019. [E-pub ahead of print] View Abstract
Hay KA, Gauthier J, Hirayama AV, Voutsinas JM, Wu Q, Li D, Gooley TA, Cherian S, Chen X, Pender BS, Hawkins RM, Vakil A, Steinmetz RN, Schoch G, Chapuis AG, Till BG, Kiem H-P, Ramos JD, Shadman M, Cassaday RD, Acharya UH, Riddell SR, Maloney DG & Turtle CJ. Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR-T cells. Blood blood-2018-2011-883710, 2019. [E-pub ahead of print] View Abstract
Hay KA. Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified (CAR-) T cell therapy. British Journal of Haematology. 2018 (accepted, in press) DOI:10.1111/bjh.15644. View Abstract
Hill JA, Li D, Hay KA, Green ML, Cherian S, Chen X, Riddell SR, Maloney DG, Boeckh M & Turtle CJ. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 131:121-130, 2018. View Publication (Open Access)
Gust J*, Hay KA*, Hanafi L-A*, Li D, Myerson D, Gonzalez-Cuyar LF, Yeung C, Liles CW, Wurfel M, Lopez JA, Chen J, Chung D, Harju-Baker S, Özpolat T, Fink KR, Riddell SR, Maloney DG, Turtle CJ. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discovery. 2017;7(12);1-16. *co-first authors. View Publication (Open Access)
Hay KA, Hanafi L-A, Li, D, Gust J, Liles, WC, Wurfel MM, Lopez JA, Chen J, Chung D, Harju-Baker S, Cherian S, Chen X, Riddell SR, Maloney DG, Turtle, CJ. Kinetics and Biomarkers of Severe Cytokine Release Syndrome after CD19 Chimeric Antigen Receptor-modified T Cell Therapy. Blood. 2017;130(21);2295-2306. View Publication (Open Access)
Turtle CJ, Hay KA, Hanafi L-A, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR, Maloney DG. Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated with CD19-Specific Chimeric Antigen Receptor–Modified T Cells After Failure of Ibrutinib. J Clin Oncol. 2017;35(26):3010-3020. View Publication (Open Access)
Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs. 2017;77(3):237–245. View Publication (Open Access)
Hay KA, Lee B, Goktepe O, Connors JM, Sehn LH, Savage KJ, Shenkier T, Klasa R, Gerrie A, Villa D. Impact of time from diagnosis to initiation of curative chemotherapy on survival of patients with diffuse large B-cell lymphoma. Leukemia and Lymphoma. 2015;57(2):276-282. View Abstract
Lee B, Goktepe O, Hay K, Connors JM, Sehn LH, Savage KJ, Shenkier T, Klasa R, Gerrie A, Villa, D. Effect of place of residence and treatment on survival outcomes in patients with diffuse large B-cell lymphoma in British Columbia. Oncologist. 2014;19(3):283–90. View Publication (Open Access)
Berry JD, Hay KA, Rini JM, Yu M, Wang L, Plummer FA, Corbett CR, Andonov A. Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology. MAbs. 2010 Jan;2(1):53-66. View Publication (Open Access)