Therapeutic vaccine for the treatment of cancer
An active cancer vaccine strategy targeting tumor-associated carbohydrate antigens expressed on tumor cells using biomimetic glyconanoparticles generated from unique red blood cells. The resulting sustained immune response inhibits tumor growth.
While envisioned already in 1891, only a few cancer vaccines have been approved by the FDA thus far. The key barriers to their success are low antigenicity of targeting antigens, tumor heterogeneity, and low mutational burden with only few peptide neoantigens in some cancers. These limitations prompted the continued search for other potential antigens for vaccines. Tumor associated glycosylation changes generate carbohydrate−neoantigens that are excellent candidate targets for immunotherapy. In particular, Neu5Gc, the antigenic non-human dietary carbohydrate that accumulates on human carcinoma, generates a whole array of cancer neoantigens.
Cancer immunotherapy aims to harness the immune system to fight cancer. Cancer cells harbor diverse modifications that lead to neoantigens, including aberrant expression of cell surface carbohydrates. Targeting tumor-associated carbohydrate antigens (TACA) holds great potential for cancer immunotherapy. Here we designed an active cancer vaccine immunotherapy strategy to target TACA-positive tumors.
We generated biomimetic glyconanoparticles to form nano-ghosts (NG) that either express (NGpos) or lack expression (NGneg) of TACA-glycoconjugates in their natural context. We show that optimized immunization of mice with NGpos glyconanoparticles induce a strong, diverse and persistent anti-Neu5Gc IgG immune response, in contrast to the control NGneg. Resulting anti-TACA IgG were also detected within Neu5Gc-positive tumors and inhibited tumor growth in-vivo. We further demonstrate that the kinetics and quality of the immune response has a major influence on the efficacy of the therapeutic cancer vaccine. Combination therapy of this cancer vaccine together with checkpoint inhibitors therapy was even more effective then each of the individual treatments. These findings reinforce the potential of TACA neoantigens as immunotherapy targets.
Provisional patent application was submitted
Reuven, E. M. et al. Biomimetic Glyconanoparticle Vaccine for Cancer Immunotherapy. ACS Nano 2019, 13, 2936-2947