CAR-modified CMV-Specific T Cell (CAR-CMVST) Solutions

As part of our commitment to making CAR-T cell therapies safe and effective, Creative Biolabs is reengineering CAR-T using CMV to create novel cell therapies for solid tumors. We plan to treat solid and hematologic tumors to reduce production costs while improving anti-tumor effects.

Introduction to Vaccine Boosting CAR-T Cells

Chimeric antigen receptor (CAR) T cells to destroy cancer cells have shown promising roles in treating certain types of cancer, such as leukemia and lymphoma. However, it does not work well in the treatment of solid tumors. Current researchers have discovered a way to overcome this obstacle by using a vaccine to boost the response of CAR T cells and help the immune system produce a new class of T cells that target specific tumor antigens. In studies with mice models, the data have suggested that this vaccine-boosting CAR-T cell approach can not only significantly enhance the killing effect of cell therapy on tumors, but also generate engineered T cell therapy targeting other tumor antigens to further enhance the killing effect on tumors. Moreover, virus-based vaccine-boosting CAR-T cells can restimulate these CAR-T cells and enhance the persistence and antitumor activity.

Fig.1 CAR T Cell Design.¹

CAR-modified CMV-specific T Cells (CAR-CMVSTs) Solutions

In the past few years, Creative Biolabs has developed a technology platform called CAR-CMVSTs (CAR-modified CMV-specific T Cells) to address the limitations of CAR/TCR t cell therapy in the treatment of solid tumors. Our technology platform is designed to transfer CBL-specific endogenous cytomegalovirus (CMV) specific T cell receptors into existing CAR T cells to provide more durable antitumor activity.

Workflow

1. Immunogenic CMV peptide is loaded onto the endogenous HLA complex of cancer cells
   CMV peptides were loaded into the endogenous HLA complex of cancer cells, allowing these cells to be recognized by specific T cells against cytomegalovirus.
2. Assembly of tumor-directed fusion proteins of CMV peptide /HLA complexes
   In general, various tumor-directed fusion proteins comprising CMV peptide–HLA complexes have been established to bind to overexpressed target antigens on the surface of cancer cells.
3. Generation of CAR-modified CMV-specific T cells
   CMV-specific T cells were selected from healthy CMV seropositive donors, stimulated by pp65 protein, and then lentiviral transduction was used to express bis-specific CAR T cells.
4. CMV-specific CAR-T costimulation and amplification
   In our labs, a series of co-stimulatory molecules, such as CD28 and 4-1BB, have been broadly used for enhancing the action and killing function of CMV-specific CAR-T cells.

Fig.2 Anti-Tumor Activity of Adoptively Transferred Bi-Specific T Cells is Enhanced by CMVpp65 Vaccination.²

How CAR-CMVSTs Solutions Can Assist Your Project

Nowadays, we have redirected CMV-specific CAR-T cells to recognize and lysate tumor cells via a range of tumor-associated targets, including but not limited to CD19 and HER2. Our unique CMV-specific CAR-T cells can maintain their ability to proliferate in response to CMV antigen stimulation and improve antitumor efficacy in B-cell malignancy models.

Creative Biolabs employs key proprietary technologies that work together to enable us to develop the most effective and safe CAR-CMVST cell therapies. Furthermore, we have generated best-in-class CMV peptide-HLA complex delivery solutions to address specific unmet needs in the field of cell therapy. We have a proprietary set of CAR engineering technologies, dual CAR and enhanced CAR, that can be combined with our CMV-peptide technology platform to further enhance the therapeutic efficacy of our CAR-T product candidates.

Creative Biolabs is developing advanced CAR-CMVST cell therapies to deliver powerful, targeted, effective novel CMV-specific CAR-T cell therapies to harness the body's immune system and cure cancer. We have 2000 sq meters of GMP facilities in the USA. Our scientists have published more than 100 peer-reviewed papers in leading international journals. If you are interested in our services, please contact us for more details. Let us know what you need and we will accommodate you. We look forward to working with you in the future.

References

1. Tian, Yonggui, et al. "Gene modification strategies for next-generation CAR T cells against solid cancers." Journal of hematology & oncology 13.1 (2020): 54.
2. Wang, Xiuli, et al. "CMVpp65 vaccine enhances the antitumor efficacy of adoptively transferred CD19-redirected CMV-specific T cells." Clinical Cancer Research 21.13 (2015): 2993-3002.