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Targeting the CD22 receptor of B-cells with chimeric antigen receptor (CAR)-T cells has been a promising new therapy to treat B-cell malignancies in clinical trials, inducing remission in 70% of patients with relapsed acute lymphoblastic leukemia (ALL). However, diminished CD22 expression on B-cell surface can lead to relapse and decreased remission duration, which may be prevented through increasing CAR-T affinity towards CD22. 

T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation.

The treatment of cancer using immunotherapies has garnered substantial attention and excitement considering the clinical benefits observed in patient populations previously refractory to treatment. Tumor infiltrating T cells can significantly impact cancer progression and immunotherapy response; however, immunosuppressive tumor microenvironments can impede antitumor T cell induction, trafficking, and local activity. Thus, personalized immunotherapy approaches have shown limited efficacy against most solid tumors.

Mesothelioma is an aggressive cancer covering anatomic surfaces (e.g. lining of the lungs, heart, abdomen, etc.) that resists multi-modality therapies. Regional recurrence of mesothelioma from residual tumor cells prevents long-term benefits after surgical resection. Furthermore, there is no clinical consensus on intracavitary adjuvants that are effective in extending the tumor reduction effect of surgery.

Hematopoietic and pluripotent stem cells can be differentiated into T cells with potential clinical utility. Current approaches for in vitro T cell production rely on Notch signaling and artificial mimicry of thymic selection. However, these approaches result in unconventional or phenotypically aberrant T cells; which may lead to unpredictable behavior in clinical use. Thus, there exists a need for improved methods of generating conventional T cells in vitro from stem cells.
 

Bladder cancer is the fifth most common cancer in the United States and one of the costliest cancers to treat. Compared to other cancer types, bladder cancer has been understudied, and there is a need for informative mouse bladder cancer models that resemble the clinical situation and allow for evaluation of chemotherapeutic or immunotherapeutic agents. The orthotopic murine bladder cancer model MB49 resembles non-muscle invasive, nonmetastatic urothelial carcinomas and provides an opportunity to study the anti-tumor effects of immune cell checkpoint inhibitors.

Peptides corresponding to transmembrane domains of a number of integral proteins were discovered to spontaneously self-assemble in aqueous solutions into stable and remarkably uniform nanoparticles.  Researchers at the NCI’s Cancer and Inflammation Program have developed fully synthetic, peptide-based, virus-like nanoparticles capable of delivering cytotoxic, radioactive, and imaging agents. 

Structure and function of tumor-target self-assembling particles:

Adoptive cell therapy (ACT) using tumor-specific T cells can produce positive clinical responses in some cancer patients. Nevertheless, several obstacles to the successful use of ACT for the treatment of cancer and other conditions remain. For example, one or more of the in vivo persistence, survival, and antitumor activity of tumor-specific T cells can, in some cases, decrease following adoptive transfer. Accordingly, there is a need for methods of obtaining a robust population of tumor-specific T cells for ACT.

Hyperthermia has been used extensively and successfully in the treatment of solid tumors. For accessible solid tumors with impressive efficacy not amenable to surgery, ablative hyperthermia (>55°C for 20 s to 15 min) has been used as a definitive treatment. By contrast, for both radiotherapy and chemotherapy, mild hyperthermia (40-45°C for up to 1 hour) has been shown useful as an adjuvant.

Cancer is the second leading cause of death worldwide. The primary cause of mortality from cancer is metastasis. While the underlying mechanisms of cancer metastasis are still being unraveled, the gp78 protein involved in ER-associated degradation (ERAD) appears to play a role in metastasis in sarcoma. Targeting gp78 may be a therapeutic option in cancer treatment.