Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

Abstract

The promise of tumor immunotherapy to significantly improve survival in patients who are refractory to long-standing therapies, such as chemotherapy and radiation, is now being realized. While immune checkpoint inhibitors that target PD-1 and CTLA-4 are leading the charge in clinical efficacy, there are a number of other promising tumor immunotherapies in advanced development such as Listeria-based vaccines. Due to its unique life cycle and ability to induce robust CTL responses, attenuated strains of Listeria monocytogenes (Lm) have been utilized as vaccine vectors targeting both infectious disease and cancer. In fact, preclinical studies in a multitude of cancer types have found Listeria-based vaccines to be highly effective at activating anti-tumor immunity and eradicating tumors. Several clinical trials have now recently reported their results, demonstrating promising efficacy against some cancers, and unique challenges. Development of the Lm-based immunotherapies continues with discovery of improved methods of attenuation, novel uses, and more effective combinatorial regimens. In this review, we provide a brief background of Listeria monocytogenes as a vaccine vector, discuss recent clinical experience with Listeria-based immunotherapies, and detail the advancements in development of improved Listeria-based vaccine platforms and in their utilization.

Molecular Characterization of CF33 Canine Cell Line and Evaluation of Its Ability to Respond against Infective Stressors in Sight of Anticancer Approaches

“…Firstly, the basal expression of genes modulating the innate immune response and regulating the cell cycle was assessed. Secondly, we evaluated this cell line’s interaction with two types of infectious stressors, which are currently studied as new anti-cancer therapies [ 31 ]. Moreover, we demonstrated that the CF33 cell line at different passages shows the same characteristics of gene expression as canine mammary carcinoma (CMC) [ 32 , 33 , 34 , 35 , 36 , 37 ].…”

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control

“…We next asked if the functional TST subset present in mice with early lesions could be harnessed to stop tumor progression. Listeria monocytogenes (LM) is a gram-positive intracellular bacterium which induces strong CD4 and CD8 T cell responses 19 . Using an actA inlB deficient attenuated LM vaccination strain 20 , which has been used in human clinical trials for advanced cancers [21][22][23] , and engineered to express the TAG epitope I (LMTAG) 5 , we tested whether early vaccination of AST;Cre-ER T2 would protect mice from liver cancer progression.…”

Colorectal cancer vaccines: The current scenario and future prospects

“…Attenuated strains of Listeria monocytogenes have been utilized as vaccine vectors targeting different tumors, especially human papillomavirus (HPV)-associated cancers, pancreatic cancer, and malignant pleural mesothelioma, improving the survival of patients ( 71 ). As for CRC, a personalized live-attenuated, double-deleted (pLADD) L. monocytogenes -based immunotherapy was designed for a phase 1 trial to analyze its safety (NCT03189030).…”