Optimizing frontline car T cell therapy in multiple myeloma
Active Project Grant Awarded Last action
- Award ID
- F31CA310546
- Recipient
-
The Regents Of The University Of Colorado UEI MW8JHK6ZYEX8 Part of The Regents Of The University Of Colorado
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $44,886
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date 0% complete
- Place of performance
- Aurora, CO 80045, USA
Award details come from USAspending.gov.
Description
- Abstract
- The objective of this study is to improve responses to chimeric antigen receptor (car) T cell therapy for patients with multiple myeloma (MM). MM is an incurable plasma cell malignancy with increasing incidence in the united states. The approval of bcma-targeting car T cell therapy was practice-changing, offering patients with MM that had become multi-drug refractory another chance. However, despite achieving deep remissions, car T cell therapy remains non-curative, with all patients inevitably relapsing. One third of patients relapse within just one year. The pre-manufacturing T cell population plays a major role in response to bcma car T cell therapy in MM. Patients with MM have T cell defects which progressively worsen with MM treatment. Efforts to improve response duration by moving car T cell therapy to second line in myeloma patients' treatment have improved progression-free survival, supporting the integration of car T cell therapy into frontline MM treatment. However, IT is unknown what effects, if any, frontline anti-MM induction therapy has on the efficacy of car T cell therapy. Preliminary data has revealed that car T cells manufactured from patients' T cells post-induction therapy are less cytotoxic than treatment-naïve T cells. This proposal aims to characterize the effect induction therapy has on MM patients' T cells and car T cell efficacy. The hypothesis is that car T cells derived from treatment- naïve MM patients will be more effective than post-induction car T cells due to a "healthier" composition of pre- manufacturing T cells. A "healthier" composition consists of higher CD4:CD8 ratios, more naïve, less exhausted T cells that functionally have greater activation, proliferation, and cytokine production. Uniquely, this proposal will utilize serial samples collected from patients at diagnosis, following 6 cycles of induction and after 6 months on immunomodulatory maintenance therapy. To my knowledge, this is the first time temporal changes in car T cell efficacy will be assessed from individual patients progressing through treatment. Aim 1 will characterize the composition and function of patients' T cells using flow cytometry and single cell transcriptomics. Aim 2 will determine how anti-MM induction impacts bcma car T cell efficacy by probing car T cell proliferation, cytokine production, cytotoxicity and in vivo depth/duration of response. The study's findings have the potential to shift the MM treatment paradigm, by supporting the collection of T cells prior to anti-MM treatment. Additionally, for the 150,000+ americans living with MM who have already been treated, these studies will inform future work aimed at restoring altered T cells back to their healthier treatment-naïve counterparts.
Quick answers
Who received award F31CA310546?
F31CA310546 was awarded to The Regents Of The University Of Colorado by National Cancer Institute (National Institutes of Health) on December 1, 2026.
How much is award F31CA310546 worth?
$44,886 has been obligated on F31CA310546.
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