T cell receptor engineered T cells are attracting tremendous interest in the treatment of epithelial cancers. Their ability to target intracellular proteome can be directed against shared tumor associated antigens, such as cancer testes antigens and viral oncoproteins. Emerging data point to clinical activity of these engineered T cells in various epithelial cancers, as well as potential mechanisms of treatment evasion that may help inform on future treatment optimizations.

Triumvira develops autologous and allogeneic T cell therapies engineered with the T cell Antigen Coupler (TAC) receptor that redirects T cells to the respective antigen on tumor cells and activates T cells by co-opting the endogenous T cell receptor complex independently of MHC. Preclinical models have shown tumor clearance with minimal toxicity. A Phase I/II trial with TAC01-HER2 for patients with solid tumors is ongoing.

Much attention has been on the potential for allogeneic cell therapeutics yet other fundamental issues remain. These include cell fitness, cell expansion and persistence, tumor heterogeneity and immunosuppression. The solutions I will discuss confront these critical issues to drive cell therapy to succeed in more hematologic cancer patients and to break through to meaningfully treat solid tumor indications.

While immunotherapies have had a revolutionary impact on cancer care, adoptive cell therapy has thus far been limited in the solid tumor space. In this talk, Carisma Therapeutics' proprietary CAR-M (chimeric antigen receptor macrophage) cell therapy platform will be reviewed, with a focus on preclinical solid tumor data and a discussion of the ongoing first-in-class, first-in-human CAR-M clinical trial evaluating CT-0508 for HER2+ solid tumor patients.

The intersection of cell biology and engineering and biomedical sciences is giving rise to next generation immunotherapies with transformative impact on cancer treatment. These approaches require analytical tool which could analyze critical functional aspects of these therapies during development and manufacturing. Agilent Technologies is well poised to support the growing number of immunotherapy workflows from early discovery to production. We will discuss these workflows, measurement modalities and new standards to inform, validate and qualify every step of the process.

TCR/BCR repertoire profiling holds great potential for understanding disease mechanisms. We introduce a novel technology for profiling of all human TCR and BCR variable regions and phenotypic characterization of immune cells in bulk and at the single-cell level in PBMCs and immune cell fractions. Preliminary data shows that TCR/BCR clonotype analysis combined with targeted expression profiling of immune cells can be applied for large-scale discovery in several immune-responsive model systems. 

Emerging data show a role for intratumoural NK cells in driving immunotherapy response and, accordingly, there have been renewed efforts to further elucidate and target the pathways controlling NK cell antitumour function. I discuss how the role of NK cells evolves with tumour progression, presenting new opportunities to target NK cell function to enhance cancer immunotherapy response rates across a more diverse range of cancers.

Natural Killer (NK) cells are innate immune cells that can eliminate target cells in an antigen-independent fashion.  NK cells can be engineered to express chimeric antigen receptors (CARs), armored to exhaustion, and expanded under optimized conditions, and gene edited to further enhance cytotoxicity, selectivity, and persistence.  Nkarta is developing off-the-shelf CAR NK cells that maximize the therapeutic potential of allogeneic NK cells alone or in combination with other agents.

Recent studies have revealed that CARs and TCRs do not need highest affinity for best performance. Instead, CAR-T cells require suboptimal cell avidity while TCR-T cells do best having high avidity to their target. Here, we’ll present the first CAR-T cell studies revealing correlation between avidity and in vivo tumor reduction and cell function, and discuss how avidity can become the key quality attribute used for cell product release to patients.

Iovance is currently conducting pivotal studies in patients with metastatic melanoma and advanced cervical cancer. In addition, the company’s TIL therapies are being investigated for the treatment of patients with locally advanced, recurrent or metastatic cancers including head and neck and non-small cell lung cancer. 

CD8+ CTL-based therapies, including CD19-targeted CAR T cell therapy, have seen substantial limitations in B cell malignancies, producing durable remissions only in less than one-half of treated patients. Here, we present a novel form of immunotherapy for B cell malignancies using multi-specific CD4+ CTLs with superior ability for in vivo persistence, and discuss results from preclinical and translational studies.

We are developing a novel immunotherapy for hepatocellular carcinoma (HCC), the most common type of liver cancer. Our approach is to re-engineer Natural Killer (NK) cells – which are native to the human immune system – to target the specific cancer cell marker CD147, and thereby kill the cancer cells more effectively and safely than existing treatments.

Orgenesis’ point of care platform (POCare) is a decentralized processing approach for cell and gene therapies. Advantages include simplified logistics, scalability, rapid response to patient needs and reduced cost. We will present our strategy incorporating mobile processing solutions to minimize physical infrastructure with integrated closed automated processing systems. We will present a case study of an adoptive cell therapy with tumor infiltrating lymphocytes for solid cancers in adult and pediatric indications.     

Phase I/II trial results of Vigil involving 233 cancer patients and 1433 doses demonstrate safety, mechanism and optimization of dose schedule. Results of Phase 2a/2b trials validate improved RFS and OS in advanced OC patients with BRCA wild-type (BRCA-wt) molecular profile and enhanced response in homologous recombination proficient (HRP) subset population. Combination therapy with atezolizumab and/or BRCA-wt/HRP subset with TP53 mutation support broad treatment application involving solid tumor malignancies.

Due to their immunocompromised status, cancer patients are at an increased risk for severe SARS-CoV-2 infection, which causes systemic injury through IL-6-mediated inflammation. We present a model to explain the mechanistic interplay between both conditions with clinical evidence. We also evaluate the efficacy of novel therapies in clinical trials, including a promising cellular therapy that received FDA fast track designation.