may enhance immunotherapy efficacy in cancer treatment.
A majority of patients with immunologically cold tumors do not benefit from current immunotherapies.
Oncolytic viruses can kill tumor cells and stimulate the immune response within the tumor microenvironment.
Initial tumor cell killing by oncolytic viruses may lead to increased release of tumor-associated antigens and recruitment of antitumoral T cells.
Preclinical studies indicate that combining oncolytic viruses with immune checkpoint inhibitors or adoptive T cell therapy could result in additive or synergistic effects.
Recent clinical trials have shown additive effects of oncolytic viruses combined with immune checkpoint inhibitors in melanoma.
The timing of oncolytic virus and immune checkpoint inhibitor administration may significantly influence treatment outcomes and requires further investigation.
Simplified
New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates.
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L Russell and R.M. Diaz are employees of and own stock/options in Vyriad. K.W. Peng and S.J. Russell own stock/options in Vyriad and are inventors of patents licensed from Mayo Clinic to Vyriad relating to oncolytic measles and vesicular stomatitis virus technology.
PubMed
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