Cancer vaccines have been in development for decades, both in animal models as well as in clinical trials. Cancer vaccines have yielded promising results in pre-clinical in vitro experimental systems and in rodent models. However, translation to the clinic has been cumbersome and although cancer vaccines have shown to be able to induce anti-tumor immune responses, clinical benefit has rarely been observed. To date, only one therapeutic cancer vaccine, Sipuleucel-T, has been approved by the FDA and EMA. However, its clinical implementation remains limited. Many other vaccines in phase III clinical studies have been discontinued due to the lack of clinical efficacy (e.g. MAGE-A3 vaccine in Melanoma and NSCLC, GVAX, Canvaxin and PROSTVAC). It has been hypothesized that several reasons could account for this lack of clinical efficacy, which include (i) the type of tumor antigen(s) used, (ii) the type of antigen-presenting cell used or targeted, (iii) the type of adjuvant used, (iv) the type of immune response induced, (v) route of administration, (vi) immunosuppressive barriers at the tumor site and (vii) the clinical setting in question.
In recent years, new insights into (i) different dendritic cell (DC) subtypes and their impact on immune responses, (ii) immunogenicity of tumor antigens and (iii) the composition of the tumor microenvironment have been elucidated. Novel findings on the immunogenicity of different DC subsets such as CD1c+ DCs, CD141+ DCs and plasmacytoid DCs, together with recent evidence of mutated neoantigen-specific immune responses, have important implications for the improvement of cancer vaccines. Moreover, our improved understanding of the tumor microenvironment will facilitate the development of rational combination therapies in conjunction with vaccines to tackle tumor treatment from different angles. These insights can guide the development of novel strategies to counter one or more of these hurdles, which can pave the way to enhance the clinical utility of cancer vaccines.
This Research Topic aims to provide a comprehensive overview of current issues regarding cancer vaccine development with an emphasis on novel approaches towards enhancing their efficacy. We seek Review, Mini-Review, Original Research, Hypothesis and Theory, Perspective, Case Report and Clinical Trial articles that cover, but are not limited to, the following topics:
1. Cancer vaccines: recent advances and remaining hurdles.
2. Cellular cancer vaccines.
3. Molecular cancer vaccines.
4. Route of administration of cancer vaccines.
5. In situ vaccination approaches.
6. Vaccination approaches targeting specific DC subtypes, including nanoparticle vaccines, for cancer treatment.
7. Vaccines targeting cancer stem cells.
8. Vaccines targeting neoantigens.
9. Positioning of cancer vaccines in clinical practice.
10. Combinatorial approaches to enhance vaccination efficacy.
Cancer vaccines have been in development for decades, both in animal models as well as in clinical trials. Cancer vaccines have yielded promising results in pre-clinical in vitro experimental systems and in rodent models. However, translation to the clinic has been cumbersome and although cancer vaccines have shown to be able to induce anti-tumor immune responses, clinical benefit has rarely been observed. To date, only one therapeutic cancer vaccine, Sipuleucel-T, has been approved by the FDA and EMA. However, its clinical implementation remains limited. Many other vaccines in phase III clinical studies have been discontinued due to the lack of clinical efficacy (e.g. MAGE-A3 vaccine in Melanoma and NSCLC, GVAX, Canvaxin and PROSTVAC). It has been hypothesized that several reasons could account for this lack of clinical efficacy, which include (i) the type of tumor antigen(s) used, (ii) the type of antigen-presenting cell used or targeted, (iii) the type of adjuvant used, (iv) the type of immune response induced, (v) route of administration, (vi) immunosuppressive barriers at the tumor site and (vii) the clinical setting in question.
In recent years, new insights into (i) different dendritic cell (DC) subtypes and their impact on immune responses, (ii) immunogenicity of tumor antigens and (iii) the composition of the tumor microenvironment have been elucidated. Novel findings on the immunogenicity of different DC subsets such as CD1c+ DCs, CD141+ DCs and plasmacytoid DCs, together with recent evidence of mutated neoantigen-specific immune responses, have important implications for the improvement of cancer vaccines. Moreover, our improved understanding of the tumor microenvironment will facilitate the development of rational combination therapies in conjunction with vaccines to tackle tumor treatment from different angles. These insights can guide the development of novel strategies to counter one or more of these hurdles, which can pave the way to enhance the clinical utility of cancer vaccines.
This Research Topic aims to provide a comprehensive overview of current issues regarding cancer vaccine development with an emphasis on novel approaches towards enhancing their efficacy. We seek Review, Mini-Review, Original Research, Hypothesis and Theory, Perspective, Case Report and Clinical Trial articles that cover, but are not limited to, the following topics:
1. Cancer vaccines: recent advances and remaining hurdles.
2. Cellular cancer vaccines.
3. Molecular cancer vaccines.
4. Route of administration of cancer vaccines.
5. In situ vaccination approaches.
6. Vaccination approaches targeting specific DC subtypes, including nanoparticle vaccines, for cancer treatment.
7. Vaccines targeting cancer stem cells.
8. Vaccines targeting neoantigens.
9. Positioning of cancer vaccines in clinical practice.
10. Combinatorial approaches to enhance vaccination efficacy.
