Experimental cancer therapies range from mRNA vaccines to engineered bacteria and CAR T cells

Scientists are working on multiple experimental strategies to fight cancer, including mRNA therapeutic vaccines, engineered probiotic bacteria that act as tumor-seeking drug factories, and an experimental CAR T-cell therapy that targets tumor macrophages. The approaches remain in early development, with personalized vaccines described as promising, engineered Escherichia coli Nissle 1917 tested in mice, and the macrophage-focused therapy producing striking results in preclinical models of metastatic ovarian and lung cancer.

Scientists are working on developing mRNA vaccines that would work to fight cancer once it’s detected. These vaccines would be considered “therapeutic vaccines” rather than preventative ones. Once you develop the cancer, you can design a vaccine that targets some of the unique proteins and other things that the cancer cells are showing to your body, and therefore your immune system can get ramped up and target those very specific cancer antigens that the cells are showing.

While some cancers have common antigens, mRNA technology could make personalized vaccines a reality. A physician could take a sample from a patient’s cancer cells and design a vaccine that targets their specific cancer. The speed in which you can make them is really unparalleled. The vaccines are in early development, but are incredibly promising. There are currently two vaccines that do work to prevent cancer: the hepatitis B vaccine given to babies and the HPV vaccine for preteens and teenagers.

Another approach uses bacteria-assisted, tumor-targeted therapy. New findings published March 17 in PLOS Biology showed that Escherichia coli Nissle 1917 (EcN) can be modified to carry anticancer compounds and target tumors in mice. The team engineered the probiotic strain so it could produce Romidepsin (FK228), an FDA-approved drug with anticancer properties, and then created a mouse model by introducing breast cancer tumor cells and treated the mice with the modified bacteria.

The experiments showed that EcN was able to accumulate inside tumors and release Romidepsin FK228 in both laboratory and live animal settings under different conditions. This allowed the bacteria to function as a targeted treatment, delivering the drug directly to tumor sites. The authors said EcN’s tumor colonization synergizes with Romidepsin’s anticancer activity to form a dual-action cancer therapy. The approach has not yet been tested in humans, and future studies will need to examine possible side effects as well as strategies for safely removing the bacteria after treatment.

Researchers also developed an experimental immunotherapy that tackles metastatic cancer by focusing on the cells that surround and shield cancer cells. The findings were published in Cancer Cell, and the therapy was tested in aggressive preclinical models of metastatic ovarian and lung cancer. Rather than attacking cancer cells themselves, the treatment focuses on tumor macrophages, immune cells that act as guardians for cancer cells.

To counter this, the research team created a therapy designed to remove tumor macrophages while leaving healthy macrophages intact. The approach uses CAR T cells, which are engineered from a patient’s own T cells, and the researchers modified the CAR T cells to release interleukin-12, a powerful immune activating molecule that stimulates killer T cells. In mice with metastatic lung and ovarian cancers, treatment with the engineered CAR T cells produced striking results. The animals lived months longer, and many were completely cured.

Analysis using advanced spatial genomics techniques showed that the therapy reshaped the tumor microenvironment. Immune suppressing cells were reduced, and immune cells capable of attacking cancer were drawn into the tumor. The researchers said studies in humans are still needed to determine whether the therapy will be safe and effective for patients, and described the findings as proof of concept rather than a cure.