Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy
Round 1
Reviewer 1 Report
The work entitled “Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy” by Wang et al. focuses on nonviral nanodelivery systems of mRNA vaccines used for cancer gene therapy and immunotherapy. Over the years many mechanisms and processes for delivering of mRNA vaccines have been uncovered; however, this is an area that continues to grow and expand, with new strategies appearing each day. This review highlights that expanding field of research and the emerging novelties.
The work is very well organized and the research aside from being pertinent, to the point and up to date is also scientifically sound. The authors did an excellent job getting deeper and deeper in their investigation. It would have been however, extremely important to have in the introduction section a sentence or a paragraph in which the author highlighted the novelty of this research and its importance compared to the many reviews already in existence, also in this field. Also, there are instances when we clearly see information being presented in sequential mode instead of a more organic way, meaning that there are instances when the authors present the information given by one author, than the other, and the other but there is little connection and that would be most important to improve the quality of the manuscript. There are also English writing mistakes that should be fixed; however, none too important to compromise the meaning and scientific quality of the information. Finally, even though the authors made a significant effort in presenting many future ideas and predictions for the field, section 7 is way too extensive, leaving the readers tired and without reaching an ideal climax after reading such a well though out manuscript. This section requires more refinement and attention and should be abbreviated.
Overall, the work is of high quality and should be considered for publication after minor revision.
Author Response
Dear Reviewer：
Thank you for your letter and for the reviewer’s comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our manuscript. We have studied comments carefully and have made correction which we hope meet with approval. The main corrections in the paper and responds to the reviewer’s comments are as following (We also uploaded an attachment):
Point 1. It would have been however, extremely important to have in the introduction section a sentence or a paragraph in which the author highlighted the novelty of this research and its importance compared to the many reviews already in existence, also in this field.
Response 1: Thank you for reading our manuscript carefully. Some sentences which highlighted the novelty of our research were added into paper and the addition begins with line 160 of the revised manuscript. The contents are as follows: On the other hand, in this review, we systematically compiled the nonviral nano-delivery systems currently used in mRNA vaccines with analysis of their advantages and disadvantages, which may help future mRNA vaccine development on vector selecting. In addition, we also comprehensively listed the mRNA cancer vaccines in various clinical trials, providing some updated information.
Point 2. Also, there are instances when we clearly see information being presented in sequential mode instead of a more organic way, meaning that there are instances when the authors present the information given by one author, than the other, and the other but there is little connection and that would be most important to improve the quality of the manuscript.
Response: Thank you for reading our manuscript carefully and your suggestion. We have tried to present the examples cited by our manuscript in a more organic way. For instance, in the section 5.1. Lipid nanoparticles (LNPs), we put examples together, which have the same stated purpose, and we add linking words/phrases between them, as shown below: Despite some insufficiencies, mRNA-loaded NPs are still potential clinical tools, as demonstrated by unprecedented rapid development of mRNA COVID-19 vaccines. To make LNPs more powerful in mRNA delivery, many scientists tried to optimize them, and there have been some new findings. For transfection efficiency, Kauffman et al. showed that increasing the ionizable lipid: mRNA weight ratio can enhance delivery efficiency [91]. Ball et al. optimized the LNP delivery system by adding a negatively charged “helper molecular” to the NP. In their study, the mRNA-loaded LNPs co-formulated with siRNA induced three-fold increases in luciferase protein expression compared to that in formulations without siRNA [92]. For endosomal escape, Herrera M. et al. found that it preferentially occurs in late endosomes, not early endosomes [93]. Maugeri M. et al. demonstrated that endosomal escape of mRNA-loaded LNPs depends on the molar ratio between the ionizable lipids and mRNA nucleotides [94]. Lee, S. M et al. studied the interaction between LNPs and a model endosomal membrane and showed that 4A3-Cit (a lipid with an unsaturated tail) exhibited superior lipid fusion over saturated lipids, suggesting that unsaturated lipids promote endosomal escape [95]. For targeted delivery, scientists have observed that the targeting functionalities of LNPs are largely related to the chemical structure of the active lipids [96]. For instance, imidazole-based LNPs preferentially target splenic T cells [97]; Zukancic et al. found that PEGylation is critical for achieving selective organ targeting, even though it is at the lowest ratio in LNPs [98]. For immunogenicity, Hassett et al. found that the particle size may influence LNP immunogenicity; they demonstrated that LNPs in smaller diameter were substantially less immunogenic in mice, but all the particle sizes tested induced a robust immune response in nonhuman primates (NHPs), suggesting that an optimal mRNA vaccine particle size as determined for rodents may not translate to primates [99]. For toxicity, previous research has shown that nonbiodegradable lipids would cause mortality in mice, whereas biodegradable and biodegradable lipids administered at a similar dose were well tolerated [100].
Point 3. There are also English writing mistakes that should be fixed.
Response: Thank you for reading our manuscript carefully and your suggestion. We have corrected all spelling errors in the manuscript (including tumour, titres, programme). We also corrected some English writing mistakes. For example, we changed “Therefore IVT mRNAs need to be designed without GC-enriched 5'-UTRs.” to “Therefore, IVT mRNAs need to be designed without GC-enriched 5'-UTRs.”. Moreover, we corrected some wrong tenses in the paper. For example, we changed “Lipid-polymer hybrid nanoparticles (LPNs) were the earliest reported example of hybrid NPs” to “Lipid-polymer hybrid nanoparticles (LPNs) are the earliest reported example of hybrid NPs”. In this revision, we have re-edited the language of the manuscript and sent it to AJE, a professional organization, for language polishing and modification. The language modification certificate is attached. The picture is shown in the attached document.
Point 4. Finally, even though the authors made a significant effort in presenting many future ideas and predictions for the field, section 7 is way too extensive, leaving the readers tired and without reaching an ideal climax after reading such a well though out manuscript. This section requires more refinement and attention and should be abbreviated.
Response: Thank you for reading our manuscript carefully and your suggestion. We shortened the section 7 by removing some contents similar to those appeared in the introduction, with the number of words reduced from 1528 to 967. In addition, we also rearranged the section 7 to present the information in a more organic way. In section 7, we followed an order of current situation, drawbacks and future direction of the mRNA cancer vaccines.
All in all, thank you very much for your valuable suggestions. We tried our best to improve the manuscript and made some changes in the manuscript. And we appreciate for your warm work earnestly, and hope that the correction will meet with approval.
Sincerely yours,
Prof Yang Li
State Key Laboratory of Biotherapy
Sichuan University, Chengdu, P. R. China
Author Response File: 
Author Response.docx
Reviewer 2 Report
The manuscript "Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy" is a review paper that reports the use of messenger RNA for cancer therapy. This is a hot topic subject in the field of nanomedicine and of great interest to the readers. I consider the manuscript is well documented and can be considered for publication in Pharmaceutics, after the authors reply. Some comments are given hereunder:
- expressions like "in vivo", "ex vivo", "in vitro" should be written in italic;
- I would suggest to cite the reference: Pharmaceutics 2021,13, 2090. https://doi.org/10.3390/pharmaceutics1312209
- where are documented the information given in Table3. The clinical trials of mRNA vaccine mediated by DC vaccines. Their origin should be given in the manuscript.
- the same comment is available for information given in Table 4.
- the figures 2 and 4 are from reference or the authors drawn them?
Author Response
Dear Reviewer：
Thank you for your letter and for the reviewer’s comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our manuscript. We have studied comments carefully and have made correction which we hope meet with approval. The main corrections in the paper and responds to the reviewer’s comments are as following (We also uploaded an attachment):
Point 1: expressions like "in vivo", "ex vivo", "in vitro" should be written in italic.
Response1: Thank you for reading our manuscript carefully. All expression like "in vivo", "in vitro", "ex vivo" in the paper have been written in italic.
Point 2: I would suggest to cite the reference: Pharmaceutics 2021,13, 2090. https://doi.org/10.3390/pharmaceutics13122090
Response 2: Thank you for reading our manuscript carefully and your suggestion. We have cited this reference in the section 4 (The principles of mRNA vaccine design and modification) of our manuscript. The contents of the reference section are shown as follows: Discovered in the 1970s, the 5'-cap structure (m7G5'ppp5'N), composed of a 7-methylguanosine nucleoside and a terminal nucleotide linked through a triphosphate bridge in the 5'-mRNA, confers IVT mRNA stability and translation efficiency [1]; and the 5'-UTR is a noncoding region, but it can help mRNA bind to ribosomes [1].
Point 3. where are documented the information given in Table3. The clinical trials of mRNA vaccine mediated by DC vaccines. Their origin should be given in the manuscript. the same comment is available for information given in Table 4.
Response3: Thank you for reading our manuscript carefully and your suggestion. All the information given in Table 3 and 4 are found in https://clinicaltrials.gov, and we also added this in the section 6 of our manuscript, just as follows: In this section, we most focus on the clinical and preclinical trials of these mRNA cancer vaccines, which can be found on the website of https://clinicaltrials.gov.
Point 4: the figures 2 and 4 are from reference or the authors drawn them?
Response4: Thank you for reading our manuscript carefully. The figure 2 was drawn by ourselves by referring to several references, and the figure 4 is from a reference [2] (Liu T, Liang Y, Huang L. Development and Delivery Systems of mRNA Vaccines. Front Bioeng Biotechnol. 2021;9:718753. Published 2021 Jul 27. doi:10.3389/fbioe.2021.718753). We also added and explained it in the annotation of figure 4, shown as bellow: Figure 4. The structure of the 5'-cap (cited from the reference [43]). The first nucleoside in the 5'-cap is usually composed of a guanine methylated at the seventh position and a ribosome (m7G) ……
All in all, thank you very much for your valuable suggestions. We tried our best to improve the manuscript and made some changes in the manuscript. And we appreciate for your warm work earnestly, and hope that the correction will meet with approval.
Sincerely yours,
Prof Yang Li
State Key Laboratory of Biotherapy
Sichuan University, Chengdu, P. R. China
Reference:
- Baptista, B.; Carapito, R.; Laroui, N.; Pichon, C.; Sousa, F. mRNA, a Revolution in Biomedicine. Pharmaceutics 2021, 13, doi:10.3390/pharmaceutics13122090.
- Liu, T.; Liang, Y.; Huang, L. Development and Delivery Systems of mRNA Vaccines. Front Bioeng Biotechnol 2021, 9, 718753, doi:10.3389/fbioe.2021.718753.
Author Response File: Author Response.docx
Reviewer 3 Report
The review paper entitled: “Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy”, is overall interesting as it deals with a topic of high clinical impact.
However, although the authors try to be exhaustive in the descriptions of the contents in the various paragraphs, the data reported in this manuscript do not provide an added value compared to those published and still available in literature, see for example https://pubmed.ncbi.nlm.nih.gov/32013049/ and https://pubmed.ncbi.nlm.nih.gov/33632261/ which have not been cited by the authors.
In order to make the review more relevant and also more updated on the main topic, i.e. use of mRNA vaccines for cancer gene therapy, the authors should improve and implement the Section 6 (Clinical mRNA vaccines for cancer therapy) to highlight the novelty of the manuscript. On the other hand, the authors should also shorten the previous sections taking into account what has already been published on the same topic.
In addition, the tumor associated antigens codified by specific mRNA vaccines used and cited by clinical trials should be specified (in the Table 3 and 4 and explained in the text) when these information are available in literature.
Author Response
Dear Reviewer：
Thank you for your letter and for the reviewer’s comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our manuscript. We have studied comments carefully and have made correction which we hope meet with approval. The main corrections in the paper and responds to the reviewer’s comments are as following （We also upload an attachment）:
Point 1: the authors should improve and implement the Section 6 (Clinical mRNA vaccines for cancer therapy) to highlight the novelty of the manuscript.
Response 1: Thank you for reading our manuscript carefully and your suggestion. To make the section 6 more complete and logical, we added some contents about the employed vectors of both DCs-based mRNA cancer vaccines and direct-injection-based mRNA cancer vaccines. In addition, we tried to add and analyse more clinical trials which have been presented in the Table 3/4 in the manuscript, including the completed, active and terminated ones.
Point 2. the authors should also shorten the previous sections taking into account what has already been published on the same topic.
Response 2: Thank you for reading our manuscript carefully and your suggestion. Taking into account the information which has already been published, we have shortened the sections from 1 to 5 by removing some contents. The number of words in the first five sections has been reduced from 8714 to nearly 6700.
Point 3. In addition, the tumor associated antigens codified by specific mRNA vaccines used and cited by clinical trials should be specified (in the Table 3 and 4 and explained in the text) when these information are available in literature.
Response 3: Thank you for reading our manuscript carefully and your suggestion. We have added the tumor associated/specific antigens codified by mRNA vaccines cited by clinical trials both in the Table 3/4 and the manuscript. In addition, some specific information about clinical trials is also added.
Table 3. The clinical trials of mRNA vaccine mediated by DC vaccines.
|
Company or institution |
Delivery vehicle |
Tumor types |
Antigens |
Phase |
Status |
NCT number |
|
Oslo University Hospital |
Not mentioned |
Prostate Cancer |
/ |
Phase I/II |
Completed |
NCT01278914 |
|
Inge Marie Svane |
Not mentioned |
Breast Cancer Malignant Melanoma |
Survivin, Htert, p53 |
Phase I |
Completed |
NCT00978913 |
|
Oslo University Hospital |
Not mentioned |
Glioblastoma Brain Tumor |
Tumor Stem Cell |
Phase I/II |
Completed |
NCT00846456 |
|
Oslo University Hospital |
Not mentioned |
Prostate Cancer |
hTERT, Survivin |
Phase I/II |
Active, not recruiting |
NCT01197625 |
|
Radboud University |
Electroporated |
Uveal Melanoma |
tyrosinase,gp100 |
Phase I/II |
Terminated |
NCT00929019 |
|
National Cancer Institute |
Not mentioned |
Leukemia |
/ |
Phase I |
Terminated |
NCT00514189 |
|
Steinar Aamdal |
Not mentioned |
Recurrent Epithelial Ovarian Cancer |
hTERT, Survivin |
Phase I/II |
Terminated |
NCT01334047 |
|
Steinar Aamdal |
Not mentioned |
Metastatic Malignant Melanoma |
hTERT, Survivin |
Phase I/II |
Terminated |
NCT00961844 |
|
Trinomab Biotech Co, Ltd. |
Not mentioned |
Brain Cancer; Neoplasm Metastases |
/ |
Phase I |
Unknown |
NCT02808416 |
|
University of Florida |
Not mentioned |
Metastatic Prostate Cancer |
hTERT |
Phase I/II |
Withdrawn |
NCT01153113 |
|
Inge Marie Svane |
Electroporated |
Prostatic Neoplasms |
PSA, PAP, survivin and hTERT |
Phase II |
Completed |
NCT01446731 |
|
Radboud University |
Electroporated |
Colorectal Cancer; Liver Metastases |
carcinoembryonic antigen |
Phase I/II |
Completed |
NCT00228189 |
|
National Cancer Institute |
Not mentioned |
Recurrent Central Nervous; System Neoplasm |
brain tumor stem cells specific mRNA |
Phase I
|
Completed |
NCT00890032 |
|
University Hospital, Antwerp |
Not mentioned |
Glioblastoma; Renal Cell Carcinoma; Sarcomas; Breast Cancers; Malignant Mesothelioma; Colorectal Tumors |
WT1 protein |
Phase I/II |
Unknown |
NCT01291420 |
|
Memorial Sloan Kettering Cancer Center |
Electroporated |
Melanoma |
Tumor-associated Antigen |
Phase I |
Active, not recruiting |
NCT01456104 |
|
Affiliated Hospital to Academy of Military Medical Sciences |
Not mentioned |
Esophagus Cancer |
MUC1 and Survivin |
Phase I/II |
Unknown |
NCT02693236 |
|
National Cancer Institute |
Not mentioned |
Malignant Neoplasms of Brain |
pp65-LAMP |
Phase I |
Active, not recruiting |
NCT00639639 |
|
University Hospital, Antwerp |
Electroporated |
Acute Myeloid Leukemia |
Wilms tumor antigen-1 |
Phase I |
Completed |
NCT00834002 |
|
Life Research Technologies GmbH |
Not mentioned |
Ovarian Epithelial Cancer |
TERT- |
Phase I |
Unknown |
NCT01456065 |
|
Memorial Sloan Kettering Cancer Center |
Electroporated |
Multiple Myeloma |
CT7, MAGE-A3, and WT1 |
Phase I |
Active, not recruiting |
NCT01995708 |
|
Radboud University |
Not mentioned |
Melanoma Stage III or IV |
gp100 and tyrosinase |
Phase I/II |
Completed |
NCT00243529 |
|
Radboud University |
Electroporated |
Hematological Malignancies |
minor histocompatibility antigens |
Phase I/II |
Completed |
NCT02528682 |
|
National Cancer Institute |
Not mentioned |
Malignant Neoplasms Brain |
cytomegalovirus (CMV) pp65-lysosomal-associated membrane protein (LAMP) |
Phase I |
Completed |
NCT00626483 |
|
Zwi Berneman |
Electroporated |
Acute Myeloid Leukemia |
Wilms' tumor antigen (WT1) |
Phase II |
Recruiting |
NCT01686334 |
|
CureVac AG |
Not mentioned |
Non Small Cell Lung Cancer |
/ |
Phase I/II |
Completed |
NCT00923312 |
|
Radboud University |
Protamine |
Prostatic Neoplasms |
/ |
Phase II |
Completed |
NCT02692976 |
|
Oslo University Hospital |
Not mentioned |
Glioblastoma |
survivin and hTERT |
Phase II/III |
Recruiting |
NCT03548571 |
|
Ludwig-Maximilians-University of Munich |
Electroporated |
Acute Myeloid Leukemia |
WT1, PRAME, and CMVpp65 |
Phase I/II |
Completed |
NCT01734304 |
|
University Hospital, Antwerp |
Electroporated |
Malignant Pleural Mesothelioma |
Wilms' Tumor Protein 1 (WT1) |
Phase I/II |
Recruiting |
NCT02649829 |
|
Asterias Biotherapeutics, Inc. |
Not mentioned |
Acute Myelogenous Leukemia |
hTERT and a portion of the lysosome-associated membrane protein LAMP-1 (LAMP) |
Phase II |
Completed |
NCT00510133 |
|
Oslo University Hospital |
Not mentioned |
Malignant Melanoma |
/ |
Phase I/II |
Completed |
NCT01278940 |
|
Radboud University |
Electroporated |
Melanoma |
gp100 and tyrosinase |
Phase I/II |
Completed |
NCT01530698 |
|
University Hospital, Antwerp |
Electroporated |
High Grade GliomaDiffuse Intrinsic Pontine Glioma |
WT1 |
Phase I/II |
Recruiting |
NCT04911621 |
|
Radboud University |
Electroporated |
Melanoma |
gp100 and tyrosinase |
Phase I/II |
Completed |
NCT00940004 |
|
Bart Neyns |
Electroporated |
Melanoma |
/ |
Phase I |
Completed |
NCT01066390 |
|
Radboud University |
Electroporated |
Melanoma |
gp100 and tyrosinase |
Phase II |
Completed |
NCT02285413 |
|
Immunomic Therapeutics, Inc. |
Electroporated |
Glioblastoma Multiforme; Glioblastoma; Malignant Glioma; Astrocytoma, Grade IVGBM |
pp65-shLAMP |
Phase II |
Recruiting |
NCT02465268 |
|
University Hospital, Antwerp |
Electroporated |
Glioblastoma Multiforme of Brain |
WT1 |
Phase I/II |
Recruiting |
NCT02649582 |
|
Gary Archer Ph.D |
Not mentioned |
Glioblastoma |
human CMV pp65-LAMP |
Phase II |
Recruiting |
NCT03688178 |
|
University Hospital, Antwerp |
Electroporated |
Acute Myeloid Leukemia |
WT1 |
Phase I |
Completed |
NCT00834002 |
|
Gary Archer Ph.D. |
Electroporated |
Glioblastoma |
Human CMV pp65-LAMP |
Phase II |
Suspended |
NCT03927222 |
|
Universitair Ziekenhuis Brussel |
Electroporated |
Malignant Melanoma |
/ |
Phase II |
Completed |
NCT01676779 |
|
Guangdong 999 Brain Hospital |
Not mentioned |
Glioblastoma |
Personalized TAAs |
Phase I |
Active, Not recruiting |
NCT02808364 |
Table 4. The clinical trials of mRNA cancer vaccine based on direct injection.
|
Company or institution |
Delivery vehicle |
Tumor types |
Antigens |
Phase |
Status |
NCT number |
|
CureVac AG |
Protamine |
Non-Small-Cell Lung cancer |
MUC1, survivin, NY-ESO-1, 5T4, MAGE-C2 and MAGE-C1 |
Phase I/II |
Completed |
NCT03164772 |
|
University Hospital Tuebingen |
Not mentioned |
Malignant Melanoma |
Melan-A, Mage-A1, Mage-A3, Survivin, GP100 and Tyrosinase |
Phase I/II |
Completed |
NCT00204516 |
|
University Hospital Tuebingen |
Protamine |
Malignant Melanoma |
Melan-A, Mage-A1, Mage-A3, Survivin, GP100 and Tyrosinase |
Phase I/II |
Completed |
NCT00204607 |
|
Merck |
Not mentioned |
Non-Small-Cell Lung cancer Pancreatic Neoplasms Colorectal Neoplasms |
mRNA-5671/V941 |
Phase I |
Recruiting |
NCT03948763 |
|
BioNTech |
Lipid-based vector |
Ovarian Cancer |
Ova |
Phase I |
Recruiting |
NCT04163094 |
|
Moderna |
Lipid-based vector |
Melanoma |
Personalized mRNA-4157 |
Phase II |
Recruiting |
NCT03897881 |
|
Moderna |
Lipid-based vector |
Solid Tumors |
Personalized mRNA-4157 |
Phase I |
Recruiting |
NCT03313778 |
|
BioNTech |
Lipid-based vector |
Prostate Cancer |
W_pro1 |
Phase I/II |
Recruiting |
NCT04382898 |
|
Universitair Ziekenhuis Brussel |
Naked mRNA |
Early-stage Breast Cancer |
/ |
Phase I |
Recruiting |
NCT03788083 |
|
National Cancer Institute |
Lipid-based vector
|
Melanoma; Colon Cancer; Gastrointestinal Cancer; Genitourinary Cancer; Hepatocellular Cancer |
Personalized mRNA |
Phase I/II |
Terminated |
NCT03480152 |
|
University Hospital Tuebingen |
Protamine |
Recurrent Prostate Cancer |
/ |
Phase I/II |
Unknown |
NCT02452307 |
|
University of Florida |
Lipid-based vector |
Adult Glioblastoma |
Autologous total tumor and pp65 full length (fl) lysosomal associated membrane protein (LAMP) |
Phase I |
Recruiting |
NCT04573140 |
|
Moderna |
Lipid-based vector |
Relapsed/refractory solid tumor malignancies or lymphoma |
human OX40L |
Phase I/II |
Active, not recruiting |
NCT03323398 |
|
BioNTech |
Lipid-based vector |
Melanoma |
NY-ESO-1, Tyrosinase, MAGE-A3, and TPTE |
Phase I |
Active, not recruiting |
NCT02410733 |
|
BioNTech SE |
Lipid-based vector |
Breast Cancer |
Tumor relevant and immunogenic RNA |
Phase I |
Active, not recruiting |
NCT02316457 |
|
CureVac AG |
Peptide-based vector |
Non Small Cell Lung Cancer |
CV9201 |
Phase I/II |
Completed |
NCT00923312 |
|
CureVac AG |
Peptide-based vector |
Non Small Cell Lung Cancer |
CV9202 |
Phase I |
Terminated |
NCT01915524 |
|
CureVac AG |
Peptide-based vector |
Prostate cancer |
CV9103 |
Phase I/II |
Completed |
NCT00831467 |
|
CureVac AG |
Peptide-based vector |
Prostate cancer |
CV9103 |
Phase I/II |
Terminated |
NCT00906243 |
|
CureVac AG |
Peptide-based vector |
Prostate cancer |
CV9104 |
Phase I/II |
Terminated |
NCT01817738 |
|
CureVac AG |
Peptide-based vector |
Prostate cancer |
CV9104 |
Phase II |
Terminated |
NCT02140138 |
|
Moderna |
Lipid-based vector |
Solid Tumor Malignancies or Lymphoma |
mRNA-2752 |
Phase I |
Recruiting |
NCT03739931 |
|
Stemirna Therapeutics |
Not mentioned |
Esophageal CancerNon Small Cell Lung Cancer |
Personalized mRNA |
Not Applicable |
Not yet recruiting |
NCT03908671 |
|
Changhai Hospital |
Not mentioned |
Advanced Esophageal Squamous; Carcinoma; Gastric Adenocarcinoma; Pancreatic Adenocarcinoma; Colorectal Adenocarcinoma |
Personalized mRNA |
Not Applicable |
Recruiting |
NCT03468244 |
|
Laura Esserman |
Not mentioned |
Carcinoma, Intraductal; Noninfiltrating |
mRNA 2752 |
Phase I |
Recruiting |
NCT02872025 |
|
University Medical Center Groningen |
Not mentioned |
Cervical Cancer |
HPV-derived tumor antigens |
Phase I |
completed |
NCT03141463 |
Additions in the manuscript:
- Moreover, Wang Q. T. et al. developed a DC vaccine against personalized TAAs to treat patients with glioblastoma multiforme (GBM) or advanced lung cancer in combination with low-dose cyclophosphamide, polyinosinic-polycytidylic acid (poly I:C), imiquimod and an anti-PD-1 antibody (NCT02808364).
- For the melanoma FixVac (BNT111), an intravenously administered liposomal RNA (encoding antigens: NY-ESO-1, Tyrosinase, MAGE-A3, and TPTE) vaccine developed by BioNTech, the data from an exploratory interim analysis showed that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediated durable objective responses (NCT02410733)
- Moreover, in a phase I trial of Vvax001 (NCT03141463), an saRNA encoding HPV-derived tumor antigens cancer vaccine against human papillomavirus (HPV)-induced cancers, immunological activity, safety, and tolerability were detected.
All in all, thank you very much for your valuable suggestions. We tried our best to improve the manuscript and made some changes in the manuscript. And we appreciate for your warm work earnestly, and hope that the correction will meet with approval.
Sincerely yours,
Prof Yang Li
State Key Laboratory of Biotherapy
Sichuan University, Chengdu, P. R. China
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
The authors have fully addressed all changes and suggestions required to improve the manuscript. In my opinion, the revised manuscript is now suitable for publication in present form.
