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City of Hope has entered into a licensing agreement with Imugene Ltd. for the patents covering a combination immunotherapy that enables CD19-directed CAR T-cell therapies to target and eradicate difficult-to-treat solid tumors. 
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BigField GEG Tech's insight:
Clinical success with chimeric antigen receptor (CAR)- based immunotherapy for leukemia has been accompanied by the associated finding that antigen-escape variants of the disease are responsible for relapse. To target hematologic malignancies with a chimeric antigen receptor (CAR) that targets two antigens with a single vector, and thus potentially lessen the chance of leukemic escape mutations, a tandem-CAR approach was investigated.
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Original Article from The New England Journal of Medicine — Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
BigField GEG Tech's insight:
Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor–modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease.
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BigField GEG Tech's insight:
City of Hope’s research on the new CAR T, published in Science Translational Medicine, offers hope for patients who have relapsed after commercially available CD19 immunotherapy treatments.
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BigField GEG Tech's insight:
This review focuses on CARs recognizing the B cell antigen CD19. Both retro- and lentiviral vectors are used encoding the different anti-CD19 CAR constructs comprising costimulatory molecules like CD28, CD137/4-1BB and OX40 either alone (2nd generation CARs) or in combination (3rd generation CARs). Current up-to-date published studies on anti-CD19 CAR therapy for acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and Non-Hodgkin lymphoma (NHL) with observed side effects are discussed and an outlook on 59 ongoing trials is given.
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Solid tumors are surrounded by an immunosuppressive tumor microenvironment. Therefore, when CAR T cells try to enter the tumor, survive, and kill the cancer cells, they cannot do so effectively.
City of Hope has therefore developed with the immuno-oncology company Imugene Ltd. a therapy combining an oncolytic virus and CAR T cells that shows preclinical potential in solid tumors and allows CD19-directed CAR T cell therapies to target and eradicate solid tumors that are difficult to treat with CAR T cell therapy alone. In this research, investigators examined the ability of the genetically engineered oncolytic virus to enter tumor cells and force CD19 protein expression on the cell surface. The results of these studies showed that truncated CD19 was expressed by the tumor cells faster than the virus was able to eradicate it; thus, this gave researchers the opportunity to target this marker with CAR T cell therapy directed against CD19. In addition, the results showed that mice that were cured of their cancer with this combination exhibited prolonged protective antitumor immunity. As a result, the researchers hope to launch a phase 1 clinical trial in 2022.