Identification of neoantigens for individualized therapeutic cancer vaccines

Lang, Franziska; Schrörs, Barbara; Löwer, Martin; Türeci, Özlem; Şahin, Uğur

doi:10.1038/s41573-021-00387-y

Cited by 285 publications

(235 citation statements)

References 281 publications

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“…Therefore, studying SMPs can help us better understand carcinogenesis, and SMPs have great potential in cancer immunotherapy. Targeting SMPs such as PD1/PD-L1 and CTLA4 has been commonly used in the clinic, including in the treatment of LSCC [ 19 – 22 ]. Using CAR T cells with cancer-specific SMPs or coupling SMPs' antibodies with chemotherapeutic agents is also developing rapidly [ 23 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma

et al. 2022

Journal of Immunology Research

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Background. This study is aimed at investigating the expressions and prognostic values of secreted or membrane-located proteins (SMPs) in laryngeal squamous cell carcinoma (LSCC). The correlations between the expressions of SMPs and immune cells’ infiltrations were also investigated. Methods. The expression data of normal laryngeal and LSCC samples were obtained from the TCGA and GEO datasets. The differentially expressed SMPs were identified, and their prognostic values were analyzed. The biological functions of differentially expressed and worse-survival-related SMPs were explored. LASSO regression, Cox multivariate analysis, and nomogram were used to construct a model to predict the survival. Then, the infiltrations of the 24 immune cell populations were calculated using the GSVA method, and the correlations between the expression of SMPs and the immune infiltration were investigated. Results. 122 samples (12 normal and 120 LSCC) of the TCGA database and 114 samples (57 normal and 57 LSCC) of GSE127165 were included. We identified that 138 SMPs were significantly upregulated in LSCC samples of both the TCGA and GEO datasets, among which 52 SMPs were significantly correlated with worse survival. GO and KEGG analyses revealed those 52 SMPs significantly participate in tumor microenvironment and immune cells’ communication. Nine of 52 SMPs (ABCC5, ATP1B3, CLEC11A, FLNA, FSTL3, MMP1, NME1, OAS3, and PHLDB2) were included in the nomogram to effectively and accurately predict the LSCC patients’ survival. The expressions of most SMPs, such as MMP1 and FSTL3, were significantly positively correlated with the immune infiltration of LSCC. Conclusions. In this study, the expression, prognostic values, and correlations with immune infiltration of SMPs were analyzed in LSCC samples. Our analyses identified several significant SMPs differentially expressed between normal laryngeal and LSCC samples, correlated with worse survival, and related to the immune infiltration.

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Section: Discussionmentioning

confidence: 99%

Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma

et al. 2022

Journal of Immunology Research

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“…mRNA vaccines are also under investigation in NSCLC. CV9201 and CV9202 are mRNA-based cancer vaccines containing sequence-optimized mRNAs encoding different cancer antigens to facilitate antigen expression and activation of the immune system, inducing an adaptive cellular and humoral immune response [ 80 , 81 , 82 ]. A previous phase I/IIa study evaluating the RNActive ® -derived CV9201 cancer vaccine in 46 patients with advanced NSCLC demonstrated an adequate safety profile.…”

Section: Current Perspectives and Future Directionsmentioning

confidence: 99%

“…A previous phase I/IIa study evaluating the RNActive ® -derived CV9201 cancer vaccine in 46 patients with advanced NSCLC demonstrated an adequate safety profile. Immune responses against all five encoded antigens (NY-ESO-1, MAGE-C1, MAGE-C2, Survivin, and TPBG) were reported [ 82 ]. CV92102, a similar RNA-based vaccine encoding 6 TAA (NY-ESO-1, MAGE-C1, MAGE-C2, Survivin, 5T4, and MUC) was also well tolerated, and antigen-specific immune responses were detected in a phase Ib study enrolling 26 patients with stage IV NSCLC [ 81 ].…”

Section: Current Perspectives and Future Directionsmentioning

confidence: 99%

Vaccine Therapy in Non-Small Cell Lung Cancer

et al. 2022

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Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes. Therapeutic cancer vaccines are designed to exploit the body’s immune system to activate long-lasting memory against tumor cells that ensure tumor regression, with minimal toxicity. A unique feature of cancer vaccines lies in their complementary approach to boost antitumor immunity that could potentially act synergistically with immune checkpoint inhibitors (ICIs). However, single-line immunization against tumor epitopes with vaccine-based therapeutics has been disappointingly unsuccessful, to date, in lung cancer. The high level of success of several recent vaccines against SARS-CoV-2 has highlighted the evolving advances in science and technology in the vaccines field, raising hope that this strategy can be successfully applied to cancer treatments. In this review, we describe the biology behind the cancer vaccines, and discuss current evidence for the different types of therapeutic cancer vaccines in NSCLC, including their mechanisms of action, current clinical development, and future strategies.

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“…Since many tumor antigens are normal proteins, the endogenous T cell repertoire usually lacks T cells with high affinity TCRs reactive with self-antigens to prevent autoimmunity. When self-reactive T cells make it through T cell development or T cells reactive with mutated self-proteins (neoantigens) are present in the periphery, they are often suppressed or exhausted in the tumor microenvironment preventing efficient tumor clearance [ 30 , 31 ]. Just as TIL are not functional in the tumor lesions but become therapeutic upon ex vivo activation and expansion, we first demonstrated that we could redirect the specificity of normal PBL-derived T cells with an HLA-A2 restricted, MART-1 reactive TCR (TIL 5) leading to recognition of HLA-A2 + MART-1 + tumor cells [ 28 ].…”

Section: Adoptive T Cell Transfermentioning

confidence: 99%

Genetic Modification of T Cells for the Immunotherapy of Cancer

et al. 2022

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Immunotherapy is a beneficial treatment approach for multiple cancers, however, current therapies are effective only in a small subset of patients. Adoptive cell transfer (ACT) is a facet of immunotherapy where T cells targeting the tumor cells are transferred to the patient with several primary forms, utilizing unmodified or modified T cells: tumor-infiltrating lymphocytes (TIL), genetically modified T cell receptor transduced T cells, and chimeric antigen receptor (CAR) transduced T cells. Many clinical trials are underway investigating the efficacy and safety of these different subsets of ACT, as well as trials that combine one of these subsets with another type of immunotherapy. The main challenges existing with ACT are improving clinical responses and decreasing adverse events. Current research focuses on identifying novel tumor targeting T cell receptors, improving safety and efficacy, and investigating ACT in combination with other immunotherapies.

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Identification of neoantigens for individualized therapeutic cancer vaccines

Cited by 285 publications

References 281 publications

Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma

Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma

Vaccine Therapy in Non-Small Cell Lung Cancer

Genetic Modification of T Cells for the Immunotherapy of Cancer

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