scholarly journals Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3408
Author(s):  
Karita Peltonen ◽  
Sara Feola ◽  
Husen M. Umer ◽  
Jacopo Chiaro ◽  
Georgios Mermelekas ◽  
...  
Keyword(s):  
Tumor Antigens ◽  
Endogenous Retrovirus ◽  
Peptide Ligands ◽  
Tumor Control ◽  
Preclinical Model ◽  
Vaccine Platform ◽  
Therapeutic Cancer Vaccine ◽  
Mhc I ◽  
Specific Tumor ◽  
Therapeutic Cancer Vaccines

Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interrogating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexible and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating immunopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.

scholarly journals Therapeutic cancer vaccines for pediatric malignancies: advances, challenges, and emerging technologies

2021 ◽  
Author(s):  
Hannah E Olsen ◽  
Geoffrey M Lynn ◽  
Pablo A Valdes ◽  
Christian D Cerecedo Lopez ◽  
Andrew S Ishizuka ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Viral Vectors ◽  
Tumor Antigens ◽  
Pediatric Population ◽  
Vaccine Platform ◽  
Therapeutic Modalities ◽  
Pediatric Cancer Patients ◽  
Outcomes For Children ◽  
Poor Outcomes ◽  
Therapeutic Cancer Vaccines

Abstract Though outcomes for pediatric cancer patients have significantly improved over the past several decades, too many children still experience poor outcomes and survivors suffer lifelong, debilitating late-effects after conventional chemotherapy, radiation, and surgical treatment. As such, there has been a renewed focus on developing novel targeted therapies to improve survival outcomes. Cancer vaccines are a promising type of immunotherapy that leverage the immune system to mediate targeted, tumor-specific killing through recognition of tumor antigens, thereby minimizing off-target toxicity. As such, cancer vaccines are orthogonal to conventional cancer treatments and can therefore be used alone or in combination with other therapeutic modalities to maximize efficacy. To date, cancer vaccination has remained largely understudied in the pediatric population. In this review, we discuss the different types of tumor antigens and vaccine technologies (dendritic cells, peptides, nucleic acids and viral vectors) evaluated in clinical trials, with a focus on those used in children. We conclude with perspectives on how advances in combination therapies, tumor antigen (e.g., neoantigen) selection, and vaccine platform optimization can be translated into clinical practice to improve outcomes for children with cancer.

scholarly journals Cancer Vaccine in Solid Tumors: Where We Stand

2021 ◽  
Vol 42 (04) ◽  
pp. 319-324
Author(s):  
Somnath Roy ◽  
Joydeep Ghosh ◽  
Ranti Ghosh
Keyword(s):  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Viral Vector ◽  
Target Selection ◽  
Immune Memory ◽  
Therapeutic Cancer Vaccine ◽  
Specific Antigens ◽  
Preclinical And Clinical Studies ◽  
Therapeutic Cancer Vaccines

AbstractCancer immunotherapy has achieved landmark progress in the field of medical oncology in the era of personalized medicine. In the recent past, our knowledge has expanded regarding how tumor cells escape from the immune system, introducing immunosuppressive microenvironments, and developing tolerance. Therapeutic cancer vaccine leads to activation of immune memory that is long-lasting, safe, and effective; hence, it is becoming an attractive method of immunotherapy. Various cancer vaccine trials in the past have taught us the types of target selection, magnitude of immune response, and implementation of appropriate technologies for the development of new successful cancer vaccines. Tumor-associated antigens, cancer germline antigens, oncogenic viral antigens, and tumor-specific antigens, also known as neoantigens, are potential targets for designing therapeutic cancer vaccines. Cancer vaccine could be cell based, viral vector based, peptide based, and nucleic acid based (DNA/RNA). Several preclinical and clinical studies have demonstrated the mechanism of action, safety, efficacy, and toxicities of various types of cancer vaccines. In this article, we review the types of various tumor antigens and types of cancer vaccines tested in clinical trials and discuss the application and importance of this approach toward precision medicine in the field of immuno-oncology.

scholarly journals Selecting Target Antigens for Cancer Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 615 ◽  
Author(s):  
Luigi Buonaguro ◽  
Maria Tagliamonte
Keyword(s):  
T Cell ◽  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Vaccine Development ◽  
T Cell Response ◽  
Therapeutic Cancer Vaccine ◽  
Memory T Cell ◽  
Heteroclitic Peptides ◽  
Therapeutic Cancer Vaccines

One of the principal goals of cancer immunotherapy is the development of efficient therapeutic cancer vaccines that are able to elicit an effector as well as memory T cell response specific to tumor antigens. In recent years, the attention has been focused on the personalization of cancer vaccines. However, the efficacy of therapeutic cancer vaccines is still disappointing despite the large number of vaccine strategies targeting different tumors that have been evaluated in recent years. While the preclinical data have frequently shown encouraging results, clinical trials have not provided satisfactory data to date. The main reason for such failures is the complexity of identifying specific target tumor antigens that should be unique or overexpressed only by the tumor cells compared to normal cells. Most of the tumor antigens included in cancer vaccines are non-mutated overexpressed self-antigens, eliciting mainly T cells with low-affinity T cell receptors (TCR) unable to mediate an effective anti-tumor response. In this review, the target tumor antigens employed in recent years in the development of therapeutic cancer vaccine strategies are described, along with potential new classes of tumor antigens such as the human endogenous retroviral elements (HERVs), unconventional antigens, and/or heteroclitic peptides.

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

scholarly journals The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients

2018 ◽  
Vol 5 (4) ◽  
pp. 87 ◽  
Author(s):  
Chris Weir ◽  
Annika Oksa ◽  
Jennifer Millar ◽  
Miles Alexander ◽  
Nicola Kynoch ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Tumor Antigens ◽  
Autologous Tumor ◽  
Tumor Vaccines ◽  
Vaccine Platform ◽  
Safety Study ◽  
Diverse Range ◽  
Canine Cancer ◽  
Ongoing Development ◽  
Vaccine Approach

Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.

scholarly journals Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1660
Author(s):  
Sara Feola ◽  
Jacopo Chiaro ◽  
Beatriz Martins ◽  
Vincenzo Cerullo
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Antigen Discovery ◽  
Future Challenges ◽  
Major Bottleneck ◽  
Therapeutic Cancer Vaccines

According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

Antibody Therapeutics for Ovarian Carcinoma and Translation to the Clinic

2018 ◽  
Author(s):  
Debra H. Josephs ◽  
Heather J. Bax ◽  
Giulia Pellizzari ◽  
James F. Spicer ◽  
Ana Montes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibodies ◽  
Tumor Antigens ◽  
Ovarian Carcinomas ◽  
Immune Effector ◽  
Effector Cells ◽  
Tumor Microenvironments ◽  
Specific Tumor ◽  
Anti Cancer ◽  
Reduced Toxicity

Despite improvements over the past decade in the treatment of ovarian cancer, many patients are at risk of recurrent disease and emerging drug resistance. The increased selectivity and reduced toxicity of molecularly targeted anti-cancer agents renders them attractive for development in ovarian cancer, and monoclonal antibodies targeting ovarian cancer-specific tumor antigens represent the largest such group investigated in this clinical setting. This chapter describes examples of monoclonal antibodies clinically evaluated for efficacy in ovarian cancer. These agents recognize molecular targets expressed on tumors or within tumor microenvironments that may be essential for tumor cell survival and proliferation. Recently, antibodies targeting checkpoint molecules on immune cells have shown efficacy in modulating anti-tumor immunity, and applications in ovarian carcinomas are evaluated. The chapter focuses on therapeutic agents’ attributes on targeting key cancer growth and progression pathways, and propensity to engender effector functions by activating immune effector cells in tumors and the circulation.

scholarly journals Identification of Tyrosinase-related Protein 2 as a Tumor Rejection Antigen for the B16 Melanoma

1997 ◽  
Vol 185 (3) ◽  
pp. 453-460 ◽  
Author(s):  
Matthew B. Bloom ◽  
Donna Perry-Lalley ◽  
Paul F. Robbins ◽  
Yong Li ◽  
Mona El-Gamil ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Tumor Antigens ◽  
Human Tumor ◽  
Human Melanoma ◽  
Tissue Differentiation ◽  
B16 Melanoma ◽  
Tumor Rejection ◽  
Site Directed Mutagenesis ◽  
Preclinical Model ◽  
Binding Motif

Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinaserelated protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.

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