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Oncolytic viral therapy is an exciting area of development for the treatment of multiple cancer types. Therapeutic efficacy of oncolytic viruses is achieved through selective amplification of virus in tumor cells causing tumor lysis and promoting immune stimulation through release of tumor antigens and viral antigens in the tumor microenvironment. However, oncolytic virus treatments encounter the humoral and cellular host immune defense mechanisms, leading to quick elimination of the oncolytic viruses and a significantly reduced therapeutic potential.

Calidi Biotherapeutics has developed a novel cell-based delivery system shown to: i) overcome the host immune defense mechanisms, ii)  amplify the oncolytic viruses, and iii)  instantly modify the tumor microenvironment leading to effective virus expansion and optimal tumor cell targeting.  Importantly, these effects are not significantly influenced by the individual tumor characteristics, making this therapeutic approach suitable for targeting multiple tumor types.

The Calidi Biotherapeutics platform leverages allogeneic stem cell loaded with vaccinia virus, which prevents the viral elimination by patient’s immune system. The vaccinia virus and virus-encoded proteins amplify inside the stem cell and facilitates initial viral amplification and expansion at the tumor sites. This process is accompanied by immunogenic cell death of cancer cells leading to efficient induction of potent anti-tumor immune responses. (See image below)

The combined effect of efficient cell-based delivery and potentiation of virus, direct eradication of cancer cells by the oncolytic viruses, and induction of anti-tumor immunity are responsible for the potent anti-tumor efficacy of this approach not only at the injected tumor site but also at distant metastatic tumor sites.

Our cell-based delivery vehicles have intrinsic immunomodulatory properties that inhibit specifically and transiently the patient’s antiviral immune responses at the tumor site. This approach eliminates or significantly reduces patient-specific rejection when used in allogeneic settings, making our treatment universal.

Calidi Biotherapeutics has also developed a method validating the use of our cells in allogeneic settings. Compatibility was verified by analyzing the ability of our cells to amplify and deliver the oncolytic virus in the presence of a patient’s immune system components. Calidi’s stem cell-based delivery platform has been shown to overcome serum-induced inactivation of oncolytic Vaccinia Virus (VV), thus dramatically enhancing the treatment efficacy. We are currently investigating multiple indications including in-transit melanoma, castrate-resistant metastatic prostate cancer, triple-negative breast cancer, and bladder cancer all non-responsive to most currently available treatments.