Translation of the novel oncolytic immunotherapy VET6-PDI

The National Cancer Institute, part of the Department of Health and Human Services, awarded $306,756 to Kalivir Immunotherapeutics, Inc. on September 3, 2026, under the Cancer Treatment Research program (CFDA 93.395) to complete translational studies necessary for clinical preparation of VET6-PDI, a novel oncolytic viral immunotherapy designed for colorectal cancer treatment.

VET6-PDI represents a next-generation oncolytic virus engineered with multiple genetic modifications and transgenes to overcome limitations of previous therapies. The virus is designed for enhanced intravenous administration and tumor-selective viral replication, with modifications that induce multiple steps in adaptive T-cell response and maintenance pathways. Previous preclinical work has demonstrated VET6-PDI's mechanism of action and potency against colorectal cancer tumors in mouse models, including both hot and cold tumor types. This work addresses a gap in available therapies: while immunotherapies have emerged as a potential treatment approach in colorectal cancer, they are limited by low response rates in certain subtypes, and no effective oncolytic virus therapies have been developed for colorectal cancer use, partly due to historical delivery constraints.

Kalivir Immunotherapeutics, Inc. is located in Blawnox, Pennsylvania. The award period extends from September 3, 2026 through August 31, 2027.

Abstract

The goal of this project is to complete much of the translational studies necessary to prepare a novel oncolytic viral (OV) therapy, VET6-PDI, for clinical evaluation in colorectal cancer (CRC). CRC is the predominate form of GI cancer, and a leading cause of cancer death in the united states. Recently, immunotherapies have emerged as a potential new treatment approach in CRC but have been limited by low response rates, especially in MSS and RAS wild type subtypes. However, the ability of OVS to exploit the immune system has been demonstrated in other solid tumor types, such as melanoma and bladder cancer, and so they hold promise for use in CRC, especially if effective systemic delivery were possible. Oncolytic viruses have the potential to incorporate multiple features into a single viral backbone, to target cancer cells directly (to induce cell death), to overcome localized immune suppression within the tumor, and to boost the anti-tumor adaptive immune response while evading anti-viral immune responses. To date, no effective OV therapies have been developed for use in CRC, partly due to the historical need to delivery most OVS directly into the tumor, a delivery mechanism that is often not feasible in disseminated colorectal cancer. VET6-PDI represents a next generation OV therapy and has been engineered to contain multiple genetic modifications and expresses several transgenes, which, collectively, overcome many of the limitations facing previous generations of OVS. Modifications in VET6-PDI allow for greatly enhanced intravenous administration, increased tumor-selective viral replication, as well as induction of multiple steps along the adaptive t-cell response and maintenance pathways. Previous pre-clinical work has demonstrated VET6-PDI's mechanism of action and potency against tumors, including mouse models of CRC, and matching hot and cold tumors. We believe this therapy has significant potential to advance the treatment of CRC, and advancing VET6-PDI to clinical testing is of importance. The work described in this current proposal is specifically aimed at completing the studies necessary to prepare for clinical evaluation. As such, we will demonstrate that our existing manufacture process can be used to create VET6-PDI at clinical grade and in sufficient quantities for use in clinical testing, with the ultimate goal of producing an economically viable product. In addition, we will complete the FDA-mandated safety and toxicology testing through a series of mouse studies. We will develop all assays necessary to confirm the clinical product (VET6- PDI) is as intended, and these will be qualified in-house. In addition a viral bank of VET6-PDI will be made and released in our cgmp facility for use as seed material in all future manufacturing runs for clinical testing as well as eventual commercial use. Finally, mouse studies will be run to help define target populations and a clinical protocol for the treatment of CRC. As a result, first in man studies will be possible soon after the completion of this proposal.