Advancements and Challenges in Personalized Neoantigen-Based Cancer Vaccines

Parminder Singh ^1,2 Mahalaqua Nazli Khatib ³ Roopashree R ⁴ Mandeep Kaur ⁵ Manish Srivastava ⁶ Amit Barwal ⁷ G. V. Siva Prasad ⁸ Pranchal Rajput ⁹ Rukshar Syed ¹⁰ Gajendra Sharma ¹¹ Sunil Kumar ¹² Muhammed Shabil ¹³ Sakshi Pandey ¹⁴ Manvinder Brar ¹⁵ Ganesh Bushi ¹⁶ Rachna Mehta ¹⁷ Sanjit Sah ^18,19 Prakasini Satapathy PhD, MPH ^20,21 Abhay M Gaidhane ^3* Shailesh Kumar Samal ^22*

• ¹ Saveetha Medical College & Hospital, Chennai, Tamil Nadu, India
• ² University of Cyberjaya, Cyberjaya, Selangor Darul Ehsan, Malaysia
• ³ Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India
• ⁴ School of Sciences, Jain University, Bengaluru, Karnataka, India
• ⁵ Vivekananda Global University, Jaipur, Rajasthan, India
• ⁶ Department of Endocrinology, NIMS University, Jaipur, Rajasthan, India
• ⁷ College of Pharmacy, Chandigarh Group of Colleges, Mohali, Punjab, India
• ⁸ Raghu Engineering College, Visakhapatnam, Andhra Pradesh, India
• ⁹ Uttaranchal University, Dehradun, Uttarakhand, India
• ¹⁰ IES Institute of Pharmacy, IES University, Bhopal, Madhya Pradesh, India
• ¹¹ New Delhi Institute of Management, New Delhi, India
• ¹² Graphic Era University, Dehradun, Uttarakhand, India
• ¹³ Noida Institute of Engineering and Technology (NIET), Noida, Uttar Pradesh, India
• ¹⁴ Center for Research Impact and Outcome, Chitkara University, Chandigarh, Punjab, India
• ¹⁵ Chitkara University (Himachal Pradesh), Baddi, India
• ¹⁶ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
• ¹⁷ Manav Rachna International Institute of Research and Studies (MRIIRS), Faridabad, Haryana, India
• ¹⁸ Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India
• ¹⁹ Korea University, Seoul, Republic of Korea
• ²⁰ Centre for Research and Development, Chandigarh University, Mohali, Punjab, India
• ²¹ Al-Mustaqbal University College, Al-Hilla City, Iraq
• ²² Institute of Environmental Medicine, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden

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.