In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14011-e14011
Abstract:
e14011 Background: Chimeric antigen receptor T-cell (CAR-T) therapy is a relatively novel regimen for the treatment of acute lymphoblastic leukemia that has already shown promising results. Two FDA-approved CAR-T therapies, Kymriah and Yescarta have an 80% success rate in sending patients into remission. However, both of these treatments require preconditioning (PC) with chemotherapy to ensure CarT expansion and engraftment. Chemotherapy severely compromises patient’s immune-system, a further economic burden up to $70K per patient due to hospitalization, and fuels side effects of CAR-T therapy such as cytokine release syndrome (CRS) and neuroedema, driven by the release of IL-6 and GM-CSF respectively. Also, up to one third of cancer patients are too frail to tolerate chemotherapy and do not qualify for potentially life-saving therapies. A single acute dose of AVM0703 induces lymphodepletion equivalent to chemotherapy, and transiently eliminates the sites in the spleen where therapeutic cells accumulate without inducing toxicities associated with chemotherapy. Methods: Mice with subcutaneously implanted melanoma were preconditioned with AVM0703 prior to treatment with a mouse Pmel CAR-T therapy. Tumor growth was tracked and spleens were analyzed after dissection for binding of labeled CAR-T cells. In a separate study, four human patients were dosed with low doses of AVM0703 and the levels of released cytokines in the blood were quantified. Results: The mice demonstrated reduced T-cell sequestration in the spleen as noted by a reduction of fluorescently labeled cells. AVM0703 alone significantly delayed tumor growth, and as PC before Pmel T-cells, dramatically improved CAR-T-driven delay of tumor growth. In humans, a significant increase in beneficial IL-2 and IL-15 was observed, as well as a lack of released IL-6. In addition, existing literature demonstrate that AVM0703 reduces the release of GM-CSF. Conclusions: AVM0703 shows efficacy as preconditioning agent in a mouse solid tumor model of melanoma, reduces the binding of CAR-T cells in the spleen, and stimulates the release of beneficial cytokines. AVM0703 could be a non-toxic, effective preconditioning agent for patients receiving CAR-T therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.e14011
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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