Our Strategy – Obtaining Immune Normalization
Strategies used to restore host antitumor immunity following cancer-mediated immune suppression are referred to as normalization. Notably, this concept does not refer to genetic deficiencies that impact the immune system. It is focused on going beyond the traditional immune enhancement strategies and working to restore balance or immune homeostasis. The overarching goal is to gain an understanding of the specific defects in anticancer immunity in order to target and fix or “normalize” them rather than induce broad, non-specific or systemic immune responses, which are associated with higher immune-associated adverse events. Overall immune normalization should lead to the development of better combinatorial approaches, resulting in successful treatment strategies and better outcomes.
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Sanmamed MF, Chen L
How will IMMUNE 3D® study immune normalization?
We have access to HLA-matched CTL and Tumor cell lines and PD-1 resistance TIL and tumors and have characterized these cell lines with B7-H1 and PD-1 expression (among other targets). By selecting the relevant cell lines we aim to customize environments that enable the study of immune normalization such as:
- Targeting Tumor Induced Immune Escape Mechanisms
- Modulating Immunity in the TME
- Resetting Immunity in the TME
IMMUNE 3D® seeks partners with capabilities to expand on our proof-of-concept data
Chemokines are heavily involved in the migration of lymphocytes and cells from early stages of development. Chemokines also have an important role in the development and maintenance of innate and adaptive immunity. Chemokines are involved in the pathobiology of chronic inflammation, tumorigenesis and metastasis, as well as autoimmune diseases. IMMUNE 3D® has established an extensive dataset of targeting chemokine and chemokine receptors and monitoring lymphocyte migration profiles in oncology using our proprietary cell lines. The chemokine profiles obtained in these studies can be applied across a broad spectrum of diseases.
Technology advancements and bioengineering of T cells have led to breakthrough therapeutics approaches such as Chimeric Antigen Receptor (CAR) T cells and T cell Receptor (TcR) that have demonstrated remarkable patient responses in oncology. The incredible success of these treatments have paved the way for further studies in other disease areas such as autoimmunity. The combination of our platform coupled with our genomic and TCR datasets we have obtained on our cell lines enables IMMUNE 3D® to identify novel or existing antigens on our T cells for further characterization and potential engineering into novel therapies.
Adhesion molecules play a major role in the recruitment of lymphocytes such as neutrophils to the site of inflammation. The activation and adhesion of lymphocytes through the endothelium is regulated by integrins and their ligands. The importance of adhesion molecules has been highlighted in rare diseases and recent studies have extended their role as potential targets in paving the way for lymphocytes to migrate through the extracellular matrix barriers. By using patient derived cells, IMMUNE 3D® can efficiently dissect and characterize the adhesion factors and integrins that may impede T cell or general lymphocyte migration as potential therapeutic targets for diseases.
Cancers often rapidly mutate and mutations in the genome can cause these malignant cells to express mutant proteins that are tumor specific and not expressed on normal cells, referred to as neoantigens. Thus, neoantigens are attractive immune targets because of their potential to elicit potent anti-tumor immune responses, albeit with lower potential for inducing autoimmunity. The 3D system can be used to uniquely expand tumor-specific T cell populations that respond to novel neoantigens. The 3D architecture provides a stringent environment for evaluating antigen presentation and in turn the migration and infiltration patterns of lymphocytes. Neoantigen presentation on tumors have been shown to play a role in the “hot” tumor environment and increase T cell infiltration. We have characterized our tumor cell lines for neoantigens and together with the HLA-matched T cell lines can observe migration patterns of lymphocytes that may yield novel receptor-ligand interactions and antigens for potential vaccine development.
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