Current Strategies for Tumor Photodynamic Therapy Combined With Immunotherapy

Photodynamic therapy (PDT) is a low invasive antitumor therapy with fewer side effects. On the other hand, immunotherapy also has significant clinical applications in the treatment of cancer. Both therapies, on their own, have some limitations and are incapable of meeting the demands of the current cancer treatment. The efficacy of PDT and immunotherapy against tumor metastasis and tumor recurrence may be improved by combination strategies. In this review, we discussed the possibility that PDT could be used to activate immune responses by inducing immunogenic cell death or generating cancer vaccines. Furthermore, we explored the latest advances in PDT antitumor therapy in combination with some immunotherapy such as immune adjuvants, inhibitors of immune suppression, and immune checkpoint blockade.

Stereotactic Body Radiotherapy Immunological Planning – Road to Abscopal Effect by Design

.This review highlights normal and tumor tissue vasculature, immunological changes, and phenotypic alterations (VIP model) as fundamental in abscopal interaction. In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward “immunological radiation planning,” i.e., radiation scheduling with abscopal effect as a vital endpoint as well. Towards this end, this manuscript presents specific diagrammatic tumor models to optimize the outcome of abscopal response in SBRT, based on the principle of the four R’s - Repair, Redistribution, Repopulation, and Reoxygenation of radiotherapy. The article highlights the importance of restricting the dose of SBRT to < 10 Gy per fraction, appropriate use of dose painting, and concomitant/delayed SBRT boost potential. Current literature indicates that immunotherapy should not precede but follow SBRT within seven days. Included is the review of integrating “cyclical” antiangiogenics, immune adjuvants/immune-metabolites as abscopal effect enhancers with SBRT. The importance of proton, carbon-ion SBRT is dealt with briefly. Proposed six fundamental requirements for augmentation of the abscopal cascade are listed. The existing exploratory results need to develop a definitive strategy amidst complex interactions in SBRT, immunotherapy, immune-adjuvants, & abscopal effects. We now have enough literature evidence to convert “abscopal by chance” to “abscopal by design” by harmonized combinatorial approach.

Harnessing the potential of Lactobacillus species for therapeutic delivery at the lumenal-mucosal interface

Lactobacillus species have been studied for over 30 years in their role as commensal organisms in the human gut. Recently there has been a surge of interest in their abilities to natively and recombinantly stimulate immune activities, and studies have identified strains and novel molecules that convey particular advantages for applications as both immune adjuvants and immunomodulators. In this review, we discuss the recent advances in Lactobacillus-related activity at the gut/microbiota interface, the efforts to probe the boundaries of the direct and indirect therapeutic potential of these bacteria, and highlight the continued interest in harnessing the native capacity for the production of biogenic compounds shown to influence nervous system activity. Taken together, these aspects underscore Lactobacillus species as versatile therapeutic delivery vehicles capable of effector production at the lumenal-mucosal interface, and further establish a foundation of efficacy upon which future engineered strains can expand.

Self-adjuvanting photosensitizer nanoparticles for combination photodynamic immunotherapy

Self-assembled nanoparticles composed of photosensitizers and immune adjuvants are reported for combination photodynamic immunotherapy to inhibit both primary and distant tumors.

Carbohydrate Immune Adjuvants in Subunit Vaccines

Modern subunit vaccines are composed of antigens and a delivery system and/or adjuvant (immune stimulator) that triggers the desired immune responses. Adjuvants mimic pathogen-associated molecular patterns (PAMPs) that are typically associated with infections. Carbohydrates displayed on the surface of pathogens are often recognized as PAMPs by receptors on antigen-presenting cells (APCs). Consequently, carbohydrates and their analogues have been used as adjuvants and delivery systems to promote antigen transport to APCs. Carbohydrates are biocompatible, usually nontoxic, biodegradable, and some are mucoadhesive. As such, carbohydrates and their derivatives have been intensively explored for the development of new adjuvants. This review assesses the immunological functions of carbohydrate ligands and their ability to enhance systemic and mucosal immune responses against co-administered antigens. The role of carbohydrate-based adjuvants/delivery systems in the development of subunit vaccines is discussed in detail.

Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several “cocktail” therapeutic formulations by mixing immunogenic cell death (ICD)–inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

UNDERSTANDING AND ADDRESSING IMMUNOSENESCENCE

Aging comes with an increased impact of infectious disease in terms of hospitalization, morbidity and mortality. This increased susceptibility to infection appears to be linked to age-related changes in the immune system and its capacity to respond to infection and vaccination. Importantly, this phenomenon occurs despite existence of pre-existing immune memory. The age-related weakening of the immune response is referred to as “immunosenescence”. Immunosenescence operates at several levels of the immune system and is multifactorial. Recent advances in systems immunology have shed new light on the immunological processes that may drive the age-related changes in immune response to infection and vaccination. However, gaps in our understanding still exist at basic and translational research levels. One approach to counteract this is the development and implementation of innovative vaccines against the pathogens with particular risks for older adults. The use of innovative immune adjuvants holds promise for the development of such vaccines.

Small Molecule NF-kB Inhibitors as Immune Potentiators for Enhancement of Vaccine Adjuvants

<p>Adjuvants are added to vaccines to enhance the immune response and provide increased protection against disease. In the last decade, hundreds of synthetic immune adjuvants have been created, but many induce undesirable levels of proinflammatory cytokines including TNF-a and IL-6. Here we present small molecule NF-kB inhibitors that can be used in combination with an immune adjuvant to both decrease markers associated with poor tolerability and improve the protective response of vaccination. Additionally, we synthesize a library of honokiol derivatives identifying several promising candidates for use in vaccine formulations. <b></b></p>