Emerging data on adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) in the treatment of lung cancer will be presented.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes has demonstrated encouraging efficacy and safety in patients with advanced melanoma and NSCLC. Next-generation TIL therapies aim to overcome suppressive barriers encountered by TIL to broaden and deepen responses in difficult to treat solid tumors, particularly in epithelial cancers. New approaches aim to enrich for less differentiated and more stem-like TIL, increase the frequency of tumor reactive cells, downregulate expression of inhibitory receptors, and express tethered cytokines to increase function and persistence.

Co-expression of CD39 and CD103 highly enrich for tumor-reactive CD8 T cells from all solid malignancies tested thus far (at least 10 tumor types). These cells also express some exhaustion markers but we can rescue their proliferative and functional capacities. Once rescued and expanded, they can kill autologous tumors in vitro and in vivo and we have FDA approval for a Phase I ACT clinical trial using these cells. We plan to start the trial in the 2nd quarter of 2023 and will target melanoma, head & neck cancer as well as other solid malignancies.

To address limitations in current TIL therapies, we are building an engineered TIL pipeline that incorporates our cytoDRiVE platform for pharmacologically-controlled protein expression. The lead candidate in our cytoTIL15 platform (OBX-115) employs controllable membrane-bound IL-15 (mbIL15) that drives IL-2 independent TIL persistence and superior efficacy in PDx models, creating an IL-2 free product. OBX-115 is being evaluated in the clinic for melanoma (NCT05470283) and preclinically for other indications.

• Monotherapies vs. Combinations​
• NK 
• Gamma deltas
• Myeloid cells

eTILs-- Revolutionizing the treatment of solid tumors via our proprietary CRISPRomics and CRISPR2 platforms. eTIL are gene-edited Tumor Infiltrating Lymphocyte (TIL) cell therapy products that have demonstrated transformational tumor-killing abilities in preclinical tumor models. We developed KSQ-001, our lead single-edit eTIL program, by applying our CRISPRomics platform to T cells to discover the top genes to inactivate with CRISPR/Cas9 with the goal of maximizing the ability of tumor-targeting T cells to destroy solid tumors. We combined our CRISPRomics platform with our CRISPR2 technology, which employs randomly-paired CRISPR guide libraries, to discover KSQ-004, our lead dual-edit eTIL program. eTILs offer the possibility of lower dosing and reduced patient conditioning when compared to other cell therapies, potentially improving the patient experience. Our simplified ExPRESS eTIL manufacturing process promises simpler and more rapid tumor-to-vein turnaround times.

Alloplex Biotherapeutics is pioneering an adoptive cell therapy that involves the in vitro training of peripheral blood mononuclear cells (PBMC) to differentiate, proliferate, and acquire tumoricidal properties against a broad range of tumor types. We have advanced this program into Phase I against multiple types of metastatic cancers. Early clinical results show SUPLEXA are safe, have activity in multiple solid tumor types, and induced pharmacodynamic changes in patient PBMC.

Despite unprecedented successes in hematologic malignancies, T cell therapies are still facing significant challenges for the treatment of solid tumors. T cell exhaustion, lack of persistence, and an immunosuppressive tumor microenvironment are among the causes for the poor success thus far. ElevateBio is leveraging synthetic biology and multiplexed base-editing approaches to target epigenetic and metabolic pathways to engineer TCR T cells with improved fitness and functions to overcome these challenges.

We described human memory-like NK cells with enhanced anti-tumor activity. We have recently demonstrated the safety and promising activity of using memory-like NK cells in AML and MDS. In my talk, I will describe key properties of the memory-like NK cells; summarize the preclinical development of the CAR-armed memory-like NK cells in ovarian and pancreatic cancer, and describe early clinical results and correlative labs from our ongoing clinical trial of cytokine-engineered allogeneic NK cells in combination with CTL4 blockade in patients with advanced head and neck

​T-Cure Bioscience is a clinical-stage TCR T company focusing on solid tumors. Our lead assets are derived from dominant TCR of extraordinary responders, i.e., 800 TCR T targeting HERV-E for stage IV non-resectable renal cell carcinoma patients who fail standard of care, and 820 TCR T targeting KK-LC-1-expressing gastric, lung, cervical, and TNBC. T-Cure has a proprietary iSORT platform that discovers “all-natural and high-affinity” TCR against customer tumor antigen/HLA combo.

The immunosuppressive tumor microenvironment (TME) of solid tumors is a barrier to cellular and immunotherapies. Myeloid cell-derived tumor associated macrophages (TAMs) accumulate in tumors but frequently are co-opted by tumor cells into supporting tumor growth. We developed the Activate, Target, Attack & Kill (ATAK) myeloid cell platform to engineer myeloid cells to recognize and phagocytize tumor cells as well as orchestrate a broad anti-tumor immune response against solid tumors.

Recent progress in understanding tumor immunity in animal models and patients with cancer has highlighted the potential of cytotoxic CD4+ T cells (CD4 CTLs) for cancer immunotherapy. Leveraging our knowledge of CD4 CTL differentiation, we developed novel approaches to producing multiantigen-targeted CD4 CTLs for immunotherapy for B cell malignancies as well as other cancers. I will present and discuss results from preclinical and translational studies. 

Allogeneic and autologous natural killer (NK) cell therapies are being actively investigated for various malignancies. Strategies to augment NK cell function and survival in patients include IL-15 stimulation. Such stimuli, however, activate ADAM17 in NK cells, which functions as a negative feedback mechanism to diminish their function. We describe a function-blocking ADAM17 mAb that greatly augments NK cell proliferation by IL-15 and the underlying mechanism, which includes CD137.

Triumvira stands out as a unique cell therapy company focused on building a strong solid tumor pipeline targeting established as well as new cancer targets, based on our proprietary, non-gene edited T cell Antigen Coupler (TAC) technology platform. This presentation will discuss: Autologous TAC01-HER2 in Phase I dose escalation study; Autologous TAC01-Claudin18.2 clinical trial will start mid-2023; Allogeneic platform based on gamma-delta TAC T cells, with first IND scheduled for H1-2024.