Glioblastoma (GBM) is one of the most common brain tumors in adults. Despite a standard-of-care including surgery and chemoradiotherapy, patients only live to a median of 15 months. This may be due to extensive spatiotemporal, intratumoral heterogeneity observed. This is thought to be created by a small population of stem-like cells marked by expression of CD133. CD133 has been shown to correlate with poor patient prognosis, metastases, relapse and worse overall survival in GBM. We thus created an anti-CD133 CAR-T therapy. Our CD133-targeting CAR-T (CART133) has shown great efficacy and in our patient-derived models of GBM. It has also exhibited safety in sparing healthy CD133-expressing cells, particularly, hematopoietic stem and progenitor cells, in our humanized model of hematopoiesis. However, in looking to the clinic, the generation of autologous CAR-Ts may be difficult as it requires sufficient numbers of a patient's own T-cells who may be immunocompromised after first-line therapy. Thus, we propose to generate allogeneic CAR-Ts that target CD133 (AlloCART133) from healthy donor T- cells. AlloCAR-T cells are genetically-edited to abrogate the T-cell receptor (TCR) to avoid graft-versus- host disease, a phenomenon in which immune-mismatch causes donor tissues to attack recipient tissues. These cells can thus be safe for a recipient while also maintaining their anti-tumor activity. AlloCART133 thus presents a clinically-relevant, off-the-shelf therapy for patients with GBM.
Citation Format: Sabra K. Salim, Jiarun Wei, Vassil Dimitrov, Katherine Chen, Chitra Venugopal, Parvez Vora, Jason Moffat, Sheila K. Singh. Systematic Generation of Allogeneic Immune-targeting Modalities for Glioblastoma [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO081.