mAbs

Context is Everything: Antibody Immunotherapy in Oncology and Autoimmunity

mAbs is pleased to welcome you to submit your research to the Article Collection "Context is Everything: Antibody Immunotherapy in Oncology and Autoimmunity".

Antibody-based immunotherapy has transformed medicine through a striking paradox: the same biological pathways can be targeted in opposite directions to treat cancer and autoimmune diseases. Checkpoint inhibitors blocking PD-1 and CTLA-4 revolutionized oncology by unleashing immune responses, while agonists of these same pathways restore tolerance in autoimmunity. This Collection explores how understanding context-dependent immune regulation is driving the next generation of antibody therapeutics. We examine antibodies that work bidirectionally across diseases alongside lessons from targets where clinical translation succeeded or failed. By focusing on shared biology, this Collection highlights how mechanistic insights from one therapeutic area illuminate opportunities in the other.

Drawing from expert insights across clinical development and translational research, this Collection examines convergent and divergent immunotherapeutic strategies in oncology and autoimmune diseases. We explore how lessons from one therapeutic area inform the other, from PD-1 pathway modulation (inhibition in cancer, agonism in autoimmunity) to broader immune cell engagement approaches.

This Article Collection examines antibody-based immunotherapeutics through a biological lens, exploring how immune cell insights translate across oncology and inflammatory & autoimmune diseases. We invite contributions across three areas:

(1) PD-1 Pathway Modulation: The PD-1 pathway exemplifies how the same target yields opposite therapeutic strategies: inhibition (anti-PD-1/PD-L1) unleashes anti-tumor immunity in oncology, while agonism expands regulatory T cells in autoimmune diseases. What do these divergent approaches reveal about context-dependent immune regulation?

(2) Regulatory T Cells and IL-2 Signaling: Tregs play opposing roles: suppressing anti-tumor immunity versus maintaining tolerance. IL-2 therapy demonstrates parallel strategies—high-dose IL-2 stimulates effector cells for cancer, while low-dose IL-2 expands Tregs for lupus and diabetes. Similarly, CCR4/CCR8 targeting depletes tumor Tregs, while CAR-Treg therapies are in trials for multiple sclerosis and lupus. How do design principles enable opposite effects through modulating the same biology?

(3) When Translation Succeeds and Fails: CTLA-4 shows successful bidirectional translation (inhibitors in cancer, agonists in autoimmunity), while TNF-α inhibitors demonstrate context-dependent effects (effective in rheumatoid arthritis but associated with increased cancer risk). What distinguishes successful translation from failed attempts? This Collection illuminates fundamental immunobiology driving next-generation therapeutic strategies across the immunotherapy landscape.

Keywords: Immune Checkpoint Modulation; Translational immunology; Autoimmunity; Cancer; Context-dependent immunity; Therapeutic antibodies

Meet the Guest Advisors

Dr. Sharmila Sambanthamoorthy is a Principal Scientist at Stealth Mode Biotech and also serves as an Assistant Editor for the journal mAbs.

Dr. Omar Duramad is a biotechnology entrepreneur, executive, and immunologist with 15+ years of experience advancing large-molecule therapeutics in oncology and immune-mediated disease. He is Co-Founder and CEO of Abmuno II, a distinguished advisor at PBSS, and previously served as Head of Large Molecule Discovery at Eli Lilly, leading cross-functional teams from target discovery through IND-enabling development across modalities including multispecific antibodies and antibody–drug conjugates. He earned a PhD in Immunology and Cancer Biology from The University of Texas MD Anderson Cancer Center and a BS in Biochemistry and Cell Biology from the University of California, San Diego, and has received honors including the Vivian L. Smith Award for Outstanding Immunologist.