Dendritic cell vaccination in melanoma patients: From promising results to future perspectives

Abstract

Dendritic cells (DCs) play an important role in the induction of antitumor immunity. Therefore, they are used as anti-cancer vaccines in clinical studies in various types of cancer. DC vaccines are generally well tolerated and able to induce antigen-specific T cell responses in melanoma patients. After DC vaccinations, functional tumor-specific T cells are more frequently detected in stage III melanoma patients, as compared to patients with advanced melanoma, indicating that the tumor load influences immunological responses. Furthermore, long-lasting clinical responses were rarely seen in metastatic melanoma patients after DC vaccination. Since more potent treatment options are available, e.g. immune checkpoint inhibitors and targeted therapy, DC vaccination as monotherapy may not be preferred in the treatment of advanced melanoma. However, encouraging results of DC vaccines combined with ipilimumab have been reported in advanced melanoma patients with an objective response rate of 38%. DC vaccines show promising clinical results in stage III patients, although clinical efficacy still needs to be proven in a phase 3 trial. The clinical and immunological results of DC vaccination in stage III melanoma patients might be further improved by using naturally circulating DCs (myeloid DCs and plasmacytoid DCs) and neoantigens to load DCs.

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

“…The lack of a univocal protocol hampers the definition of standard procedures, but, above all, does not allow for a realistic comparison among different preclinical and clinical studies. Regardless of the regimen applied, DC vaccination is characterized by a very favorable toxicity profile [180]. Nevertheless, several clinical studies have pointed to the limitations of DC-based protocols despite the ability of DC-based vaccines to elicit measurable immunological responses, whereby this approach fails to generate effective and lasting clinical antitumor responses, especially when used as monotherapy [181].…”

Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function

“…Many successes have transpired in recent years including the use of check-point inhibitors such as anti-PD-1 and anti-CTLA-4 which support sustained T cell function in the tumor microenvironment (Yun, Vincelette, Green, Wahner Hendrickson, & Abraham, 2016). Additionally direct injection of immune cells such as DC vaccines and adoptive T cell transfer therapy have gained momentum in recent years (Boudewijns et al, 2016; Yang et al, 2016). However, the success rate of these therapies vary dramatically and the mechanisms regulating these variances are poorly understood.…”

“…Additionally, alcohol can up-regulate signaling pathways which can be detrimental in the generation and activation of immune responses providing protection from tumor development such as MAPK, AKT and SGK (Ebert et al, 2016; Goral et al, 2004; Ho et al, 2012; Huang et al, 2015; Morelli et al, 2010). Given the recent rise in use and promise of immune therapies for cancer, this may be an important aspect to consider when deciding on an appropriate treatment regimen (Boudewijns, Bloemendal, Gerritsen, de Vries, & Schreibelt, 2016; Linch & Redmond, 2016). In the current study, we demonstrate for the first time that ethanol has a significant influence on DC from female but not male activation and effector function of tumor-Ag specific T cells.…”

Experience of the safety evaluation of the cellular immunotherapy application on basis LAC for canine oncological diseases treatment

“…В частности, для лечения фолликулярной и диффузной неходжкинских лимфом применяют препарат ритуксимаб, который представляет собой химерные моноклональные антитела, специфичные к CD20 -антигену, обнаруживаемому на мембране B-лимфоцитов [1]. В составе комплексного лечения пациентов с меланомой, как в медицине человека, так и в ветеринарной практике, применяется вакцина на основе дендритных клеток, индуцирующая активацию иммунного ответа, опосредуемого Т-лимфоцитами [2]. Как было показано в серии исследований in vitro и in vivo, ДК способны активировать в организме как неспецифический, опосредуемый НК, так и специфический противоопухолевый иммунный ответ, опосредованный Т-лимфоцитами [3].…”

“…of the Russian Federation; Head Physician of the veterinary clinic "Biocontrol" (evg-kornyushenkov@yandex.ru), D. E. Mitrushkin 1,2 , PhD in Biology Sc., senior researcher of the Clinic of Experimental Therapy by FBSI "N. N. Blokhin National Medical Research Center of Oncology' under the Ministry of Health of the Russian Federation; pathologist of the veterinary clinic " Biocontrol" (89035718861@mail.ru), D. V. Garanin 2 , PhD in Biology Sc., leading surgeon of the veterinary clinic "Biocontrol" (dmi-garanin@yandex.ru), A. L. Kuznetsova 1,2 2 Veterinary Сlinic "Biocontrol" (24 / 10, Kashirskoye sh., Moscow, RF, 115478). 3…”