Therapeutic vaccines for colorectal cancer: The progress and future prospect

Shahnazari, Mina; Samadi, Pouria; Pourjafar, Mona; Jalali, Akram

doi:10.1016/j.intimp.2020.106944

Cited by 36 publications

(57 citation statements)

References 172 publications

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“…As expected, LPD nanoliposomes could activate DCs and T cells, resulting in high cytotoxic effect against CT-26 cells. It is well known that the anti-tumor effect of tumor vaccines depends on their effective presentation of tumor antigens to sensitize and induce specific CTLs (Shahnazari et al, 2020 ). Hence, tumor vaccines based on predetermined tumor antigen face the inherent risk of inefficient antigen presentation, resulting in immunosuppression and potential immune evasion.…”

Section: Discussionmentioning

confidence: 99%

Tumor RNA-loaded nanoliposomes increases the anti-tumor immune response in colorectal cancer

Dai

Yin

et al. 2021

Drug Delivery

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Purpose: Tumor RNA vaccines can activate dendritic cells to generate systemic anti-tumor immune response. However, due to easily degraded of RNA, direct RNA vaccine is less effective. In this study, we optimized the method for preparing PEGylated liposom-polycationic DNA complex (LPD) nanoliposomes, increased encapsulate amount of total RNA derived from CT-26 colorectal cancer cells. Tumor RNA LPD nanoliposomes vaccines improved anti-tumor immune response ability of tumor RNA and can effectively promote anti-tumor therapeutic effect of oxaliplatin. Methods: Total tumor-derived RNA was extracted from colorectal cancer cells (CT-26 cells), and loaded to our optimized the LPD complex, resulting in the LPD nanoliposomes. We evaluated the characteristics (size, zeta potential, and stability), cytotoxicity, transfection ability, and tumor-growth inhibitory efficacy of LPD nanoliposomes. Results: The improved LPD nanoliposomes exhibited a spherical shape, RNA loading efficiency of 9.07%, the average size of 120.37 ± 2.949 nm and zeta potential was 3.34 ± 0.056 mV. Also, the improved LPD nanoliposomes showed high stability at 4 C, with a low toxicity and high cell transfection efficacy toward CT-26 colorectal cancer cells. Notably, the improved LPD nanoliposomes showed tumor growth inhibition by activating anti-tumor immune response in CT-26 colorectal cancer bearing mice, with mini side effects toward the normal organs of mice. Furthermore, the effect of the improved LPD nanoliposomes in combination with oxaliplatin can be better than that of oxaliplatin alone. Conclusion:The improved LPD nanoliposomes may serve as an effective vaccine to induce antitumor immunity, presenting a new treatment option for colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Tumor RNA-loaded nanoliposomes increases the anti-tumor immune response in colorectal cancer

Dai

Yin

et al. 2021

Drug Delivery

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“… under investigation in clinical trials In mice 69.1% of colorectal carcinoma-bearing was suppressed [ 127 ] pCEA/HBsAg DNA Promoting a promising immune system under investigation in clinical trials No detectable CEA- antibodies was seen in patients [ 120 ] CEA66 DNA DNA Stimulation of Cellular and humeral response against CEA under investigation in clinical trials 75% of showed detectable CEA immune responses. [ 128 ] NCI 4650 (mRNA 4650) RNA Immunostimulants Moderna Therapeutics safe and induce CD8 and CD4 T cell responses [ 129 ] RO7198457 (RG 6180) RNA Immunostimulants BioNTech Safe and neoantigen-specific immune responses [ 130 ] mRNA 4157 RNA m-RNA 4157 Indoctrination for peptides containing exclusive mutations (i.e., neoantigen) present in each patient’s specific tumor. Moderna’s /Merck Safe, well tolerated and T cell responses [ 131 ] DC-CEA RNA tumor antigen-encoding mRNA was transfected to autologous dendritic cells Moderna immunogenicity was tolerated suitable [ 132 ] V 941 (mRNA 5671) RNA This vaccine contains epitopes for KRAS mutations (G12D, G12V, G13D, and G12C T cell immune responses.…”

Section: Therapeutic Gene Vaccines For Crcmentioning

confidence: 99%

Recent Advances on Immune Targeted Therapy of Colorectal Cancer Using bi-Specific Antibodies and Therapeutic Vaccines

et al. 2021

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Colorectal cancer (CRC) is a universal heterogeneous disease that is characterized by genetic and epigenetic alterations. Immunotherapy using monoclonal antibodies (mAb) and cancer vaccines are substitute strategies for CRC treatment. When cancer immunotherapy is combined with chemotherapy, surgery, and radiotherapy, the CRC treatment would become excessively efficient. One of the compelling immunotherapy approaches to increase the efficiency of CRC therapy is the deployment of therapeutic mAbs, nanobodies, bi-specific antibodies and cancer vaccines, which improve clinical outcomes in patients. Also, among the possible therapeutic approaches for CRC patients, gene vaccines in combination with antibodies are recently introduced as a new perspective. Here, we aimed to present the current progress in CRC immunotherapy, especially using Bi-specific antibodies and dendritic cells mRNA vaccines. For this aim, all data were extracted from Google Scholar, PubMed, Scopus, and Elsevier, using keywords cancer vaccines; CRC immunotherapy and CRC mRNA vaccines. About 97 articles were selected and investigated completely based on the latest developments and novelties on bi-specific antibodies, mRNA vaccines, nanobodies, and MGD007.

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“…These have shown mixed results with limited efficacy in improving clinical outcomes. 70 Toll-like receptor (TLR) agonists, especially TLR7/TLR8, are currently under investigation for their immunostimulatory properties and could offer a combination strategy with cancer vaccine as an adjuvant-like signal. 71…”

Section: Tumor Vaccinationmentioning

confidence: 99%

Advances and new frontiers for immunotherapy in colorectal cancer: Setting the stage for neoadjuvant success?

Sumransub

Vantanasiri

Prakash

et al. 2021

Molecular Therapy - Oncolytics

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Immunotherapy in the metastatic setting has drastically altered the landscape of treatment for various types of malignancy, including colorectal cancer. The category of immune checkpoint inhibitors has especially emerged as a class of therapy predicated on a more comprehensive understanding of immune cell-cancer cell regulation and evolution of the tumor microenvironment over time. Strategies including adoptive cellular therapies, tumor vaccines, and antibodies have also demonstrated the ability to enhance antitumor immunity. In this article, we provide a comprehensive review of the current landscape of immunotherapeutic strategies in colorectal cancer and provide insight into how these strategies may evolve in the next decade and be adapted to more localized forms of cancers of the colon and rectum. We provide particular focus on various combination approaches under investigation for reversing cancer-induced immunosuppression, especially in mismatch repair-proficient/microsatellite-stable colorectal tumors. Finally, we summarize current understanding on a recently identified integral factor in local immune regulation, the colonic microbiome. The aim of this article is to identify current challenges and barriers to improvement and to specify opportunities for applying knowledge in the immunotherapy sphere to rational design of clinical trials intended to improve survival and related outcomes in patients treated in the neoadjuvant setting.Development of CRC involves complex processes accumulating genetic mutations, resulting in the heterogeneity of response to treatment (Figure 2). The use and approval for ICIs in CRC are thus far predicated on expression deficient mismatch repair (dMMR) with MSI-H based on landmark trials published in the past decade; however, of all patients with CRC, only 5%-15% of this population have tumors with this predictive biomarker, leaving the vast majority

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Therapeutic vaccines for colorectal cancer: The progress and future prospect

Cited by 36 publications

References 172 publications

Tumor RNA-loaded nanoliposomes increases the anti-tumor immune response in colorectal cancer

Tumor RNA-loaded nanoliposomes increases the anti-tumor immune response in colorectal cancer

Recent Advances on Immune Targeted Therapy of Colorectal Cancer Using bi-Specific Antibodies and Therapeutic Vaccines

Advances and new frontiers for immunotherapy in colorectal cancer: Setting the stage for neoadjuvant success?

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