The new immunotherapy against cancer is promising in the first tests

Much research on cancer immunotherapy focus on the use of T lymphocytes we knew that other types of immune cells could also play an important role in the fight against cancer, "says Ashish Kulkarni of the University of Massachusetts at Amherst . Now, he and his colleagues at Brigham and Women's Hospital, along with others, report that in preclinical models, they can boost the immune responses of macrophages against cancer by using a self-assembling supramolecule.

As immune cells, macrophages usually eat foreign invaders. Even cancer cells, says Dr. Kulkarni, but one of the two types does not always do it. Macrophage-type M1s are anti-tumorigenic, but M2 can be recruited by tumor cells to help them develop. In addition, tumor cells overexpress a protein that tells macrophages "do not eat me". In this way, pro-tumorigenic macrophages can represent 30 to 50% of the tumor mass, explains the biomedical engineer and lead author of the new study.

Dr. Kulkarni adds: "With our technique, we reprogram M2 in M1 by inhibiting the M2 signaling pathway, and realized that if we could rehabilitate macrophages and inhibit the protein" do not eat me, "we could tilt the balance between M1 and M2, increase the ratio of M1 to the inside of the tumor and inhibit tumor growth.In the current online edition of Nature Biomedical Engineering

To address both the M2 problem of "reeducation" and to improve the ability of macrophages to eat tumor cells, the researchers used what they call a bi-functional or "one-two" punch. Dr. Kulkarni said he and research technician Anujan Ramesh, along with colleagues in India and at Brigham and Women's Hospital at Harvard Medical School, were using a multi-component supramolecular system that would self-regulate. organizes to the nanoscale to deliver an inhibitor of antibodies and a drug to the inside of the tumor. "It's the first time that any one combines these two drugs, a drug that targets M2 macrophages and an antibody that inhibits" do not eat me the signal, "in a delivery system," notes the Dr. Kulkarni

. We believe that this new approach provides a complementary approach that can be used with other therapies. We have tested it in preclinical models of melanoma and breast cancer, two aggressive cancers, and we plan to try it on different types of cancer and in combination with other current therapies like the Therapies based on T lymphocytes used clinically. "

The researchers tested supramolecular treatment in animal models of both forms of cancer by comparing it directly with a currently available clinical drug.Mice that have not been treated have formed large tumors at the same time. The mice treated with currently available therapies showed a decrease in tumor growth at day 10, but the mice treated with the new supramolecular therapy had a complete inhibition of tumor growth. reported an increase in survival and a significant reduction in metastatic lymph nodes.

Co-author Shiladitya Sengupta at Brigham and Women's Hospital says, "We can actually see macrophages eating cancer cells," citing images of confocal microscopy shows the macrophages engulfing cancer cells

Dr. Kulkarni says that Stepwise steps are to continue testing the new therapy in preclinical models to evaluate safety, effectiveness, and dosage. The supramolecular therapy they have designed has been approved and they hope to put treatment into clinical trials if preclinical tests continue to show promise.