Magic™ Anti-CSPG4 polyclonal antibody [Biotin]

Chordoma is a locally aggressive primary malignancy of the axial skeleton. The gold standard for treatment is en bloc resection, with some centers now advocating for the use of radiation to help mitigate the risk of recurrence. Local recurrence is common, and salvaging local failures is quite difficult. Chemotherapy has been ineffective and small molecule targeted therapy has had only marginal benefits in small subsets of patients with rare tumor phenotypes or refractory disease. Recent successes utilizing immunotherapy in a variety of cancers has led to a resurgence of interest in modifying the host immune system to develop new ways to treat tumors. This review will discuss these studies and will highlight the early studies employing immune strategies for the treatment of chordoma.

The advent of CD19-specific chimeric antigen receptor (CAR) T cells has proven to be a powerful asset in the arsenal of cancer immunotherapy of acute lymphoblastic leukemia and certain B cell lymphomas. However, a sizable portion of patients treated with CD19-CAR T cells relapse with CD19-negative cancer cells, necessitating the quest for back-up antigens. Chondroitin sulfate proteoglycan 4 (CSPG4) expression has been reported on leukemic blasts bearing the ill-fated MLL 11q23 rearrangement. We aimed at exploring the use of CSPG4-specific CAR T cells against mixed-lineage leukemia (MLL)-rearranged leukemic blasts, using the precursor B cell leukemia cell line KOPN8 (MLL-MLLT1 translocation) as a model. First, we confirmed CSPG4 expression on KOPN8 cells. Bulk T cells electroporated with mRNA encoding a CSPG4-specific CAR upregulated activation markers and secreted the Th1 cytokines TNF and IFN in an antigen-specific manner upon co-culture with KOPN8 cells. More importantly, CSPG4-specific CAR T cells evinced specific degranulation towards KOPN8 cells and specifically lysed KOPN8 target cells in chromium lysis experiments. CSPG4 is a well-established CAR target in cutaneous melanoma. Here, we provide proof-of-principle data for the use of CSPG4-specific CAR T cells against MLL-translocated leukemias.