Qamar Abuhassan
1 
, Kamel Saleh
2* , S. Renuka Jyothi
3, Radhamadhab Sahoo
4, P. Prakash
5, Gunjan Mukherjee
6, Aashna Sinha
7, Turabek Boyqulov
81 Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan, Amman, 11942, Jordan
2 Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan
3 Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
4 Department of Otorhinolaryngology (ENT), IMS and SUM Hospital, Siksha 'O' Anusandhan, Bhubaneswar, Odisha-751003, India
5 Department of Biotechnology, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
6 University Institute of Biotechnology, Chandigarh University, Mohali, Punjab, India
7 School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India
8 Department of Medicine, Termez University of Economics and Service, Termez, Uzbekistan
Abstract
Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body’s most immunologically constrained ecosystems, the eye’s immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmatically regulated within ocular tissue. We synthesize recent advances in bispecific T-cell engagers, oncolytic viro-immunotherapy, mRNA and dendritic-cell vaccines, and engineered CAR/TCR-T platforms, highlighting how they collectively reconfigure the ocular tumor microenvironment from immune-silent to immune-responsive. Logic-gated antibodies, ROS-responsive nanocarriers, and CRISPR-assisted checkpoint reprogramming are added to the notion of "precision immune engineering". These developments are intended to temporarily alter immune privilege without sacrificing visual quality. Lastly, we suggest a systems-level model for ocular immuno-oncology 2.0, where immune privilege is not an unchangeable barrier but rather a configurable circuit for therapeutic orchestration. One element of a dynamic, closed-loop immune-engineering architecture is checkpoint inhibition. This platform offers the possibility of long-lasting, vision-preserving disease treatment by combining AI-driven neoantigen detection, liquid-biopsy feedback loops, and flexible delivery biomaterials. While several of these approaches remain at a conceptual or early translational stage, they outline a plausible roadmap toward vision-preserving immunotherapy in ocular oncology.