Immunogenic oncolysis by tigilanol tiglate.

Tigilanol tiglate is an oncolytic small molecule that is undergoing clinical trials. A recent study revealed the capacity of this pyroptosis inducer to elicit hallmarks of immunogenic cell death. In addition, intratumoral injection of tigilanol tiglate can sensitize subcutaneous cancers to subsequent immune checkpoint inhibitors targeting CTLA-4 alone or in combination with PD-1.

Targeted opening of the blood-brain barrier facilitates doxorubicin/anti-PD-1-based chemoimmunotherapy of glioblastoma.

Doxorubicin is a prototypical inducer of immunogenic cell death (ICD) that sensitizes to subsequent immunotherapy by PD-1 blockade. However, this systemic drug combination fails against glioblastoma, hidden behind the blood-brain barrier (BBB). A recent work delineates a biophysical method for BBB permeabilization that yields effective preclinical effects of chemoimmunotherapy.

Single-cell analysis of T lymphocytes infiltrating colorectal carcinoma: the dilemma of specificity.

Advances in single-cell RNA and T cell receptor (TCR) sequencing allow to study the specificity and functionality of tumor-infiltrating T lymphocytes. A recent study unravels fundamental differences between microsatellite-instable (MSI) colorectal cancers, in which T cells tend to be tumor-specific, and microsatellite-stable (MSS) cancers, in which T cells exhibit bystander features.

Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.

Oncolytic viruses (OVs) represent a novel class of cancer immunotherapy agents that preferentially infect and kill cancer cells and promote protective antitumor immunity. Furthermore, OVs can be used in combination with established or upcoming immunotherapeutic agents, especially immune checkpoint inhibitors, to efficiently target a wide range of malignancies. The development of OV-based therapy involves three major steps before clinical evaluation: design, production and preclinical testing. OVs can be designed as natural or engineered strains and subsequently selected for their ability to kill a broad spectrum of cancer cells rather than normal, healthy cells. OV selection is further influenced by multiple factors, such as the availability of a specific viral platform, cancer cell permissivity, the need for genetic engineering to render the virus non-pathogenic and/or more effective and logistical considerations around the use of OVs within the laboratory or clinical setting. Selected OVs are then produced and tested for their anticancer potential by using syngeneic, xenograft or humanized preclinical models wherein immunocompromised and immunocompetent setups are used to elucidate their direct oncolytic ability as well as indirect immunotherapeutic potential in vivo. Finally, OVs demonstrating the desired anticancer potential progress toward translation in patients with cancer. This tutorial provides guidelines for the design, production and preclinical testing of OVs, emphasizing considerations specific to OV technology that determine their clinical utility as cancer immunotherapy agents.