Listeria monocytogenes as a Vector for Cancer Immunotherapy: Current Understanding and Progress

Abstract

Listeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria-based vaccines induce potent antitumor immunity and the current state of Listeria-based cancer vaccines in clinical trials.

Why isListeria monocytogenessuch a potent inducer of CD8+ T‐cells?

“…The observation that L. monocytogenes induces T‐cell‐mediated immunity suggested to numerous investigators that it might represent a highly amenable and potent recombinant vaccine vector for the induction of CMI (Goossens, Milon, Cossart, & Saron, ; Ikonomidis, Paterson, Kos, & Portnoy, ; Shen et al, ). Indeed, L. monocytogenes ‐based vaccines have been developed as therapeutic vaccines for cancer immunotherapy that have shown promising results in clinical trials (Flickinger, Rodeck, & Snook, ). Below, we describe the biological features of L. monocytogenes that make it such as potent inducer of CMI.…”

“…ActA mutants grow normally within the cytosol of infected cells but are incapable of cell-to-cell spread and are approximately 1,000-fold less virulent in mouse models (Brundage, Smith, Camilli, Theriot, & Portnoy, 1993). However, unlike LLO-minus mutants, which are poor inducers of CMI, ActA mutants are extremely potent inducers of CMI and are the primary basis of attenuation used in vaccine strains safely administered to humans (Flickinger et al, 2018).…”

“…L. monocytogenes engineered to secrete tumour-associated antigens can effectively treat established tumours in mice and the therapeutic response depends greatly on CD8+ T-cells (Brockstedt et al, 2004). This approach has also proven safe in humans and has led to several clinical trials, some of which are ongoing (Flickinger et al, 2018;Maciag, Radulovic, & Rothman, 2009).…”

From cellular microbiology to bacteria‐based next generations of cancer immunotherapies

“…Is it also possible that bacteria‐induced tumour death increases the tumour‐antigen spread, contributing also to tumour detection and elimination by the immune system (Gulley et al, ). Similarly, the ability of bacteria to induce potent immune responses could be used in novel cancer immunotherapies using modified bacteria expressing tumour antigens as antitumour vaccines (Flickinger et al, ; Sedighi et al, ).…”

“…The potent activation of the immune system induced by attenuated strains of L. monocytogenes (Goossens, Milon, Cossart, & Saron, 1995) together with the ability of Listeria to induce potent CD8 +dependent responses to chimeric antigens expressed by the bacterium (Ikonomidis, Paterson, Kos, & Portnoy, 1994) set the basis to test the potential use of L. monocytogenes expressing tumour antigens in antitumoral therapy (Flickinger, Rodeck, & Snook, 2018).…”