Reprogramming CAR-T cell therapies with mRNA technology could supercharge immune cells to fight cancer, autoimmune, and other diseases while also offering a compelling solution to the persistent manufacturing challenges hindering the widespread adoption of CAR-T cell therapies.
The Promise of CAR-T Cells & mRNA Technology
CAR-T cell therapies have demonstrated remarkable success in treating hematological cancers and lymphomas. By genetically modifying a patient’s T cells to express Chimeric Antigen Receptors (CARs) targeting specific cancer antigens, these therapies have achieved unprecedented outcomes. However, their full potential is hindered by intricate manufacturing processes—often time-consuming, difficult to scale, and expensive. This bottleneck impedes their accessibility and affordability, limiting the broader impact they could have on patient outcomes.
Enter mRNA technology—a promising solution to the manufacturing challenges facing CAR-T cell therapies. By encoding CARs into mRNA and delivering them directly into T cells, we can bypass the complex ex vivo manipulation and expansion processes. This streamlined approach enhances efficiency and cost-effectiveness, allowing for the in vivo generation of CAR-T cells within a patient’s own body. The implications are profound, potentially extending the reach of CAR-T cell therapies beyond hematological cancers and lymphomas to address solid tumors and other diseases.
Groundbreaking Studies and Findings
Pioneering studies, such as the work by Billingsley and colleagues, have identified effective lipid nanoparticle (LNP) formulations for delivering mRNA into human T cells. The use of LNPs, particularly the C14-4 formulation, has demonstrated comparable CAR expression levels to traditional electroporation methods, significantly reducing cytotoxicity. This innovative approach simplifies the engineering of CAR-T cells, paving the way for more efficient and safer therapies.
Furthermore, research by Parayath and team showcased the potential of mRNA-based injections to elicit CAR-T cells within the body. Their injectable nanocarrier successfully reprogrammed circulating T cells to recognize tumor antigens, leading to disease regression in various mouse models. This breakthrough highlights the versatility and efficacy of mRNA technology in the field of cancer immunotherapy.
A Handful of Biotechs Paving the Way
- Moderna, a biotech known for pioneering the field of mRNA medicine through the success of their mRNA Covid-19 vaccine, announced its intentions to launch up to 15 new products across cancer, rare disease, and infectious disease and advance up to 50 mRNA medicines into clinical trials over the next five years.
- Capstan Therapeutics is delivering mRNA-encoded CARs to specific subsets of immune cells, engineering them to eliminate pathogenic cells that express antigens recognized by the CAR. By delivering mRNA-encoded gene editing machinery to pathogenic cells, they can modify the cells’ DNA to treat genetic disease.
- Myeloid Therapeutics’ novel in vivo engineering platform targets and activates myeloid cells within solid tumors to elicit broader anti-tumor adaptive immunity — without the need for ex-vivo cell engineering. Their mRNA technologies utilize myeloid cells to engulf cancer cells, produce anti-tumor agents, promote anti-tumor adaptive immunity, and alter the tumor microenvironment.
- Orna Therapeutics’ technology has a breadth of applications across multiple disease areas including cancer, regenerative medicine, protein replacement, infectious diseases, and autoimmunity. Their lead program is an in situ CAR therapy that combines oRNA molecules and proprietary lipid nanoparticles (LNPs) to deliver chimeric antigen receptors (CARs) directly to patient’s immune cells within the body (isCAR therapy).
- Carisma Therapeutics, a biotech developing a proprietary cell therapy platform focused on engineered macrophages, is partnering with Moderna to utilize their in vivo mRNA delivery technology to discover, develop and commercialize in vivo engineered chimeric antigen receptor monocyte (CAR-M) therapeutics for the treatment of cancer.
A Bright Future for Cancer Therapy
In conclusion, the convergence of CAR-T cells and mRNA technology holds great promise for the future of immunotherapy treatments for cancer and other diseases. The potential to overcome manufacturing challenges, broaden the applicability of CAR-T cell therapies, and enhance their efficacy against solid tumors is a beacon of hope in the relentless pursuit of more accessible and effective cancer treatments and beyond.
