How It Works

Sindbis viral vectors (SV Vectors) target and kill cancer cells by simultaneously activating the subject’s immune system and targeting specific tumors. CYN102, our lead SV vector candidate, targets late-stage ovarian cancer in rats/mice.  There are currently no adequate treatments for late-stage ovarian cancer. This experimental therapy pairs a Sindbis vector with a tumor-associated antigen (TAA), NYESO-1, to promote a memory T cell response. NYESO-1 is naturally found in  approximately 25–45% of human melanoma, lung, esophageal, liver, gastric, prostate, ovarian, and bladder cancers and approximately 80% of synovial sarcomas. NYESO-1 expression is associated with the more highly aggressive ovarian tumors.

Why is This Revolutionary?

Mechanistically, the combination of systemically administered SVs and immunomodulatory antibodies markedly changes the transcriptome signature and metabolic program of T cells, driving the development of highly activated, terminally differentiated, effector T cells. These metabolically reprogrammed T cells demonstrate enhanced tumor infiltration capacity as well as anti-tumor activity throughout the body, overcoming the repressive tumor microenvironment (TME). This represents an important step forward in treating tumors with low mutational load (i.e., neoantigens) and few tumor-infiltrating lymphocytes (TILs) (“cold” tumors).

While epithelial ovarian cancers (EOCs) are “immunogenic tumors” that produce spontaneous antitumor immune responses detectable in peripheral blood, and the presence of TILs in tumors and ascites of patients is associated with improved survival, a number of factors in the TME impair the presence or activity of TILs in EOC, thereby facilitating cancer progression. “Armed” SV vectors overcome many of the limitations of checkpoint inhibitors and agonistic mAbs by remodeling tumors to encourage immune cell infiltration and by making administration of antagonistic/agonistic mAbs more effective.

The SV vectors transit through the lymph nodes where they also actuate and recruit an immune response to trigger cell death of tumor cells through activated NK cells, macrophages and tumor antigen specific CD8+ T cells. In addition, Sindbis-mediated apoptosis and cell death releases tumor associated antigens (TAAs) from tumor cells, leading to epitope spreading. The Sindbis virus naturally binds to the high affinity laminin receptors (LAMR) that are over-expressed in tumor cells and trigger apoptosis (programmed cell-death).


It is expected that Sindbis will most often be injected systemically through Intravenous therapy (IV), however in cases where IV therapy will not work for the patient it could be administered through Intraperitoneal injection (IP). A major benefit of IV and IP treatment options is that they do not require intra-tumoral injections. Systemic administration is natural for the Sindbis virus path, which makes it possible and easy to reach tumors, metastases, possibly major organs of the body, and metastatic tumor cells.

In pre-clinical animal studies, the Sindbis treatment platform has demonstrated up to a 90% reduction in cancer and a near complete decrease and prevention of tumor recurrences. Sindbis vectors elicit a long-term memory response that makes the treated hosts resistant to tumor re-challenge. While it is is effective without payload it has enhanced anti-tumor activity with various payloads.