Neoantigens: The Novel Precision Cancer Immunotherapy
Round 1
Reviewer 1 Report
Neoantigens: the novel precision cancer immunotherapy – a REVIEW
The manuscript by Zhang et al, is a descriptive review article portraying the significance of neoantigens (tumor-specific antigens) as potential “baits” used by the emerging cancer specific immunotherapies to develop anti-cancer therapy.
The article introduces what neo-antigens are and how they are formed in cancer cells spontaneously. It describes how their non-self nature is capable of generating an immune response. The article emphasizes on the difference between neoantigens and TAA’s well in the introduction, further highlighting the former more useful in eliciting an immune response. Through the course of the manuscript, the authors define the timeline of neoantigen discovery, exploration of peptide development, catering to their use ultimately as immunotherapy.
The paper has been very well written in concise language, explaining in simple terms what neoantigens are and their potential as a immunotherauptic agent. However, the immunotherapies these neoantigens have been used for have only been listed with not much description regarding the same. I would request the authors to elaborate more on the immunotherapies utilizing the immunogenic potential of these neoantigens.
Author Response
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Reviewer 2 Report
The authors comprehensively discuss the evolution of Neoantigens in cancer immunotherapy, outlining the history of neoantigens, its design and development, and clinical studies. The authors also discuss the challenges of clinical applications and potential solutions.
Overall, the manuscript is very well-written and organized. I have a few minor comments.
1. TILs need to be abbreviated on first appearance.
2. Line 71-75: The suboptimal T cell therapeutic efficacy has been postulated to be related to the functional restraint of T cells that 74 can potentially harm the self tissues by the host.
The statement is unclear and can be reworded to simplify from readers perspective.
3. Line 318: Authors have mentioned Gao et al. as a notable example. This article needs to be cited as well. Likewise, other notable examples discussed in the manuscript must be cited.
4. Authors are advised to avoid self-citation when possible.
4. A list of all abbreviations/key terms used in the article would be helpful for readers.
5. Since the authors discussed studies on neoantigens in immunotherapy, it could be helpful for readers to see a table of clinical trials evaluating neoantigens.
Well-written, minor grammatical errors can be eliminated.
Author Response
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Reviewer 3 Report
The authors provide a historical overview of neoantigen discovery and selection for integration into immunotherapy strategies. They further discuss the process for current steps towards neoantigen-based immunotherapy, and provide a selected overview of ongoing clinical studies. Overall, the manuscript provides a nice overview of the field that could be useful for people not familiar with neoantigens, but does not offer many details or new insights for people familiar with the field.
Specific comments include,
1. The authors emphasize peptide-based neoantigen vaccines in their review, but other vaccine backbones have been used. In fact, one of the first neoantigen vaccine clinical studies used dendritic cells (Carreno B et al, 2015).
2. The section “Neoantigen design and development” (p.4) should probably include histology in the multidisciplinary approach, as tissues need to be validated for the presence of tumor/tumor-rich areas, and prepped accordingly.
3. Section 5 “Neoantigen Validation” (p.6) would benefit from references and some discussion of plusses/minuses of the various techniques; their sensitivity, and perhaps feasibility.
4. The paragraph on “Studies of neoantigens in immunotherapy” (p.6+7) ends with the authors mentioning two challenges: identification of optimal neoantigens, and ensuring consistent manufacturing. It would be informative to know how many neoantigens per vaccine are currently found to be immunogenic (on average), and what the authors think is required to optimize that number. Also, what exactly are the concerns regarding manufacture?
5. In Conclusion and discussion, the authors state that neoantigen vaccines are costly. Could they provide details on how much neoantigen vaccines cost, and how this relates to alternatives, e.g. immune checkpoint blockade?
6. There does not seem to be a call out to Figure 1. Moreover, Fig 1 emphasizes adoptive cell therapy instead of more mainstream forms of neoantigen-based immunotherapy that are discussed in the manuscript.
Minor editing of English language required
Author Response
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