Genetic Engineering Publications - GEG Tech top picks

Genetically modified immune cells successfully target specific cancer cells that may be responsible for the relapse of acute myeloid leukemia (AML). In a study published on 28 April in Nature Communications, the researchers developed a CAR T cell therapy (UCART123) targeting CD123, which is found on leukemia stem cells and enables T cells to seek out and attack cancer cells. When the team tested the UCART123 cells in a mouse model of AML, they found that the therapy effectively eliminated leukemia cells and prolonged survival. The scientists also devised a highly sensitive monitoring strategy to detect any residual cancer cells and assess the persistence of UCART123 cells. Finally, they demonstrated that UCART123 cells have specificity against leukemia cells, with minimal toxicity to normal blood cells in mice. The preclinical results led to a Phase 1 clinical trial testing UCART123 in patients with relapsed/refractory AML at several sites across the US, including New York-Presbyterian/Weill Cornell Medical Center. The results of the preclinical study suggest that UCART123 cells are highly selective and specific in targeting AML. 

A collaborative study led by the Monash Biomedicine Discovery Institute has discovered a new immune checkpoint that could be exploited for cancer treatment. The study shows that by inhibiting the protein tyrosine phosphatase PTP1B in T cells, the body's immune response to cancer can be mobilized, helping to suppress tumor growth. Indeed, this study showed that using a new drug candidate, the abundance of PTP1B in tumor-infiltrating T cells is increased, limiting the ability of T cells to attack tumor cells and fight cancer. These findings identified PTP1B as an intracellular brake, or checkpoint, reminiscent of the PD-1 cell surface checkpoint whose blockade has revolutionized cancer treatment. Furthermore, beyond the improved response to PD-1 blockade, the authors showed that inhibition of PTP1B also significantly improved the efficacy of cell-based therapies using CAR T cells. The authors demonstrate that deletion or inhibition of PTP1B can significantly improve the ability of CAR T cells to attack solid tumors in mice, including breast cancer.  

CAR T-cell therapy and antibody treatments are two types of targeted immunotherapies that have revolutionized the fields of cancer care. However, there are still significant challenges in identifying cancer cell surface proteins as targets for immunotherapies. A research group at Lund University in Sweden is well on their way as they have developed a new precision medicine technology that allows for comprehensive mapping of the entire tumor cell surface antigen landscape in patients. The method developed by the research team, "Tumor Surfaceome Mapping, TS-MAP," allows direct analysis of all accessible tumor cell surface antigens in patient tumor tissue. In a close collaboration between neurosurgery, oncology and advanced proteomics in Lund, the researchers were able to identify several tumor cell surface antigens in fresh tissue from patients with aggressive brain tumors for which there is currently no effective treatment. An important advantage of the TS-MAP technology is that it provides a complete picture of the cell surface antigens displayed on the surface of the cancer cell, as well as information about specific cell surface antigens that have a high capacity to infiltrate cancer cells, and can destroy them from within. 

Allogene Therapeutics develops allogeneic CAR T cell-based therapies for a range of hematological and solid cancers. Two candidates are being developed using Allogene's exclusive Allo CAR T platform : 

• - ALLO-316 is an AlloCAR T ™ anti-CD70 candidate in development for the treatment of renal cell carcinoma as well as several haematological cancers that express the CD70 cell surface antigen. CD52 is also disrupted in order to make CAR T cells resistant to this treatment. Allogene announced that the FDA has approved a phase 1 clinical trial in patients with advanced or metastatic renal cell carcinoma. This is the company's first clinical trial in solid tumours.  
• - ALLO-605 is a TurboCAR ™, under development for multiple myeloma, targeting B cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells. The company presented preclinical data that demonstrated improved cytokine secretion, polyfunctionality, improved in vitro serial killing activity, and improved anti-tumor activity and survival compared to CAR T cells targeting BCMA in a mouse model aggressive for multiple myeloma. Allogene revealed that it expects to file our first Investigational New Drug application for its new TurboCAR technology ™ in the first half of 2021.