Advancements and challenges in personalized neoantigen-based cancer vaccines

Parminder Singh^#^{1

2}, Mahalaqua Nazli Khatib³, Roopashree R⁴, Mandeep Kaur⁵, Manish Srivastava⁶, Amit Barwal⁷, G V Siva Rajput⁸, Pranchal Rajput⁹, Rukshar Syed¹⁰, Gajendra Sharma¹¹, Sunil Kumar¹², Muhammed Shabil¹³, Sakshi Pandey¹⁴, Manvinder Brar¹⁵, Ganesh Bushi¹⁶, Rachana Mehta¹⁷, Sanjit Sah^{18

19

20}, Khang Wen Goh^{2

21}, Prakasini Satapathy^#^{22

23}, Abhay M Gaidhane^#²⁴, Shailesh Kumar Samal²⁵

Affiliations

¹ Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
² Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia.
³ Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
⁴ Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁵ Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, India.
⁶ Department of Endocrinology, NIMS University, Jaipur, India.
⁷ Chandigarh Pharmacy College, Chandigarh Group of College, Mohali, Punjab, India.
⁸ Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, India.
⁹ School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India.
¹⁰ IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, India.
¹¹ New Delhi Institute of Management, Tughlakabad Institutional Area, New Delhi, India.
¹² Department of Microbiology, Graphic Era (Deemed to be University), Dehradun, India.
¹³ Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India.
¹⁴ Centre of Research Impact and Outcome, Chitkara University, Rajpura, Punjab, India.
¹⁵ Chitkara Centre for Research and Development, Chitkara University, Solan, Himachal Pradesh, India.
¹⁶ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
¹⁷ Clinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, India.
¹⁸ Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, Maharashtra, India.
¹⁹ Department of Public Health Dentistry, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, Maharashtra, India.
²⁰ Department of Medicine, Korea Universtiy, Seoul, Republic of Korea.
²¹ Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia.
²² University Center for Research and Development, Chandigarh University, Mohali, Punjab, India.
²³ Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, Iraq.
²⁴ Jawaharlal Nehru Medical College, and Global Health Academy, School of Epidemiology and Public Health, Datta Meghe Institute of Higher Education, Wardha, India.
²⁵ Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

^# Contributed equally.

PMID: 40160263
PMCID: PMC11949952
DOI: 10.3389/or.2025.1541326

Review

Advancements and challenges in personalized neoantigen-based cancer vaccines

Parminder Singh et al. Oncol Rev. 2025.

. 2025 Mar 14:19:1541326.

doi: 10.3389/or.2025.1541326. eCollection 2025.

Authors

Affiliations

¹ Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
² Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia.
³ Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
⁴ Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁵ Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, India.
⁶ Department of Endocrinology, NIMS University, Jaipur, India.
⁷ Chandigarh Pharmacy College, Chandigarh Group of College, Mohali, Punjab, India.
⁸ Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, India.
⁹ School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India.
¹⁰ IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, India.
¹¹ New Delhi Institute of Management, Tughlakabad Institutional Area, New Delhi, India.
¹² Department of Microbiology, Graphic Era (Deemed to be University), Dehradun, India.
¹³ Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India.
¹⁴ Centre of Research Impact and Outcome, Chitkara University, Rajpura, Punjab, India.
¹⁵ Chitkara Centre for Research and Development, Chitkara University, Solan, Himachal Pradesh, India.
¹⁶ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
¹⁷ Clinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana, India.
¹⁸ Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, Maharashtra, India.
¹⁹ Department of Public Health Dentistry, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune, Maharashtra, India.
²⁰ Department of Medicine, Korea Universtiy, Seoul, Republic of Korea.
²¹ Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia.
²² University Center for Research and Development, Chandigarh University, Mohali, Punjab, India.
²³ Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, Iraq.
²⁴ Jawaharlal Nehru Medical College, and Global Health Academy, School of Epidemiology and Public Health, Datta Meghe Institute of Higher Education, Wardha, India.
²⁵ Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

^# Contributed equally.

PMID: 40160263
PMCID: PMC11949952
DOI: 10.3389/or.2025.1541326

Abstract

Advancements in personalized neoantigen-based cancer vaccines are ushering in a new era in oncology, targeting unique genetic alterations within tumors to enhance treatment precision and efficacy. Neoantigens, specific to cancer cells and absent in normal tissues, are at the heart of these vaccines, promising to direct the immune system specifically against the tumor, thereby maximizing therapeutic efficacy while minimizing side effects. The identification of neoantigens through genomic and proteomic technologies is central to developing these vaccines, allowing for the precise mapping of a tumor's mutational landscape. Despite advancements, accurately predicting which neoantigens will elicit strong immune responses remains challenging due to tumor variability and the complexity of immune system interactions. This necessitates further refinement of bioinformatics tools and predictive models. Moreover, the efficacy of these vaccines heavily depends on innovative delivery methods that enhance neoantigen presentation to the immune system. Techniques like encapsulating neoantigens in lipid nanoparticles and using viral vectors are critical for improving vaccine stability and delivery. Additionally, these vaccines contribute towards achieving Sustainable Development Goal 3.8, promoting universal health coverage by advancing access to safe and effective cancer treatments. This review delves into the potential of neoantigen-based vaccines to transform cancer treatment, examining both revolutionary advancements and the ongoing challenges they face.

Keywords: cancer immunotherapy; immunogenicity prediction; neoantigen-based vaccines; personalized medicine; vaccine delivery systems.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**FIGURE 1**
Comparison of traditional cancer therapies and cancer immunotherapy: efficacy and side effects.

**FIGURE 2**
Transcriptomic mechanisms leading to neoantigen production in cancer.

**FIGURE 3**
Workflow for identifying tumor-specific neoantigens for personalized cancer immunotherapy.

**FIGURE 4**
Comparing neoantigen-based therapies: **(A)** Bispecific antibodies, **(B)** TCR-T, **(C)** CAR-T, and **(D)** Vaccines.

**FIGURE 5**
Challenges in developing personalized cancer vaccines.

See this image and copyright information in PMC

References

1. Savsani K, Dakshanamurthy S. Novel methodology for the design of personalized cancer vaccine targeting neoantigens: application to pancreatic ductal adenocarcinoma. Diseases (2024) 12(7):149. 10.3390/diseases12070149 - DOI - PMC - PubMed
1. Li YF, Hou QQ, Zhao S, Chen X, Tang M, Li L. Identification of tumor-specific neoantigens and immune clusters of hepatocellular carcinoma for mRNA vaccine development. J Cancer Res Clin Oncol (2023) 149(2):623–37. 10.1007/s00432-022-04285-7 - DOI - PMC - PubMed
1. Prabhakar PK, Upadhyay TK, Sahu SK. mRNA-based cancer vaccines: a novel approach to melanoma treatment. In: Advances in immunology. Academic Press; (2024).
1. Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat Rev Clin Oncol (2021) 18(4):215–29. 10.1038/s41571-020-00460-2 - DOI - PMC - PubMed
1. Li Y, Qi J, Liu Y, Zheng Y, Zhu H, Zang Y, et al. High-throughput screening of functional neo-antigens and their specific T-cell receptors via the jurkat reporter system combined with droplet microfluidics. Anal Chem (2023) 95(25):9697–705. 10.1021/acs.analchem.3c01754 - DOI - PubMed

Publication types

Actions

LinkOut - more resources

Full Text Sources
- Frontiers Media SA
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Advancements and challenges in personalized neoantigen-based cancer vaccines

Affiliations

Advancements and challenges in personalized neoantigen-based cancer vaccines

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources