Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

Abstract

This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system, followed by the antitumor response and finalizing with the consequential impact on patients’ overall survival. Today this cascade of clinical endpoints is the backbone for active immunization assessment and moreover the concept of cancer vaccines, applied in the NSCLC setting, is just evolving as a complex therapeutic strategy, in which the opportunities for cancer vaccines start from the selection of the target cancer hallmark, followed by the vaccine formulation and its platforms for immune potentiating, also cover the successful insertion in the standard of care, the chronic administration beyond progression disease, the personalization based on predictors of response and the potential combination with other targeted therapies.

Oncolytic Vaccinia Virus in Lung Cancer Vaccines

“…OVs are considered as powerful therapeutic agents as they provide good efficacy, fewer side effects, and are less harmful to cancer patients. Currently, several viruses, including vaccinia virus, coxsackievirus, adenovirus, reovirus, herpes simplex virus, measles virus, and maraba virus, are being investigated for use in the treatment of different types of advanced cancers [18,19,51].…”

“…Oncolytic VV has been intensively investigated in many preclinical and clinical studies and has shown promising results [73,74]. The therapeutic efficacy of VV can be further enhanced via genetic engineering by replacing the vTk or VGF gene with targeted therapeutic genes or via the combination with different cancer therapies, such as chemotherapy or radiotherapy [19,61]. In our previous study, we designed a novel oncolytic virus (NOV) by substituting both the vTk and VGF regions with TRAIL and Ang1, respectively, in the VV Wyeth strain genome.…”

“…In our previous study, we designed a novel oncolytic virus (NOV) by substituting both the vTk and VGF regions with TRAIL and Ang1, respectively, in the VV Wyeth strain genome. Subsequently, the anti-tumor activity of NOV was dramatically enhanced, which was shown in the increased oncolytic efficacy in 14 cancer cell lines and in a colorectal cancer (CRC) syngeneic mouse model [19].…”

“…The effectiveness of VV-based therapies has been demonstrated in a wide range of cancer types in many studies. Moreover, the research using VV as a potent immune adjuvant for therapeutic cancer vaccines in NSCLC has been focused on inducing robust anti-tumor immune responses against tumors [15,18,19]. Therefore, in this review, we will focus on the recent applications of VV on the treatment of NSCLC and discuss future opportunities of this novel strategy.…”

Immunotherapies and Combination Strategies for Immuno-Oncology

“…Cancer vaccine combinations with chemotherapy face challenges in the clinical application of treatment. Factors such as immunosuppressive tumor microenvironment, advanced age, or disease stage can significantly affect patient outcomes [ 83 ]. Personalized combinations based on predictors of responses and tumor molecular phenotypes may aid in generating better responses and overcome some of the general challenges associated with the combination of cancer vaccines with chemotherapies [ 83 ].…”