en بیوانفورماتیک Bioinformatic پژوهشي Research <strong>Background</strong>: Leukemia inhibitory factor (LIF) and LIF receptor (LIFR) are critical mediators of cellular processes, including immune regulation, stem cell maintenance, and tumor progression. In Oncology, aberrant LIF/LIFR signaling promotes tumor survival and immune evasion. This study presents the computational design of a novel chimeric vaccine targeting immunogenic epitopes derived from human LIF and LIFR.&nbsp;<br> <strong>Materials and Methods</strong>: We employed comprehensive in silico methods to investigate the biochemical characteristics, immunogenic epitopes, and potential functional domains of LIF and LIFR. After identifying suitable regions and designing a chimeric vaccine, physicochemical properties and 3D structure were predicted using various bioinformatics tools, both individually and in combination.&nbsp;<br> <strong>Results</strong>: The results showed highly antigenic B-cell and T-cell epitopes within LIF (amino acids 70-100) and LIFR (amino acids 700-780), as indicated by a VaxiJen score of 0.9737. A multi-epitope construct was engineered by fusing selected epitopes with flexible GGGGS linkers to enhance immunogenicity and structural stability.&nbsp;<br> <strong>Conclusion</strong>: A computationally designed chimeric vaccine targeting LIF and LIFR is a promising cancer immunotherapy strategy. Also, success requires rigorous in vivo validation and optimization, highlighting computational biology&rsquo;s role in cancer treatment innovation and targeting key pathways. Bioinformatics, Cancer immunotherapy, Chimeric vaccine, Leukemia inhibitory factor (LIF)/LIF receptor® 189 202 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1453-1&slc_lang=en&sid=1 Zahra Ghanei Z.Ghanei@alzahra.ac.ir 100319475328460013458 100319475328460013458 Yes Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran. Fatemeh Sefid sefid.fateme@yahoo.com 100319475328460013459 100319475328460013459 No Department of Biology Sciences, School of Materials Engineering and Interdisciplinary Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.