Typically, the starting dose in a Phase 1 trial is too low to show efficacy. For CDR Life, observing immunological activity and biomarker improvement in their very first patient was a rare and remarkable event that provided the first tangible sign their scientific platform could become a real therapeutic.

Future cancer vaccines may target antigens derived not from standard coding regions, but from the "dark genome." Dr. Radvanyi highlights that retro-transposable elements and endogenous retroviruses, activated in cancer, represent a vast, untapped source of tumor-specific antigens for novel immunotherapies.

The industry's focus on antibodies, which are easy to generate, may be a case of technology dictating the science. Dr. Radvanyi argues that natural ligand-receptor interactions, which often rely on lower affinity and higher avidity, could offer a more nuanced and effective way to modulate immune pathways than high-affinity agonist antibodies.

The current boom in immunology and autoimmune (I&I) therapeutics is not a separate phenomenon but a direct consequence of capital and knowledge from immuno-oncology. Many of the same biological pathways are being targeted, simply modulated down (for autoimmune) instead of up (for cancer), allowing for rapid therapeutic advancement and platform reuse.

The excitement around ICOS agonists for activating effector T-cells ignored a critical biological nuance: ICOS is also highly expressed on suppressive T-regulatory cells. Dr. Radvanyi notes this oversight led to therapies that inadvertently activated the very cells they aimed to overcome, a cautionary tale on scientific dogma.

While the field focuses heavily on T-cells and myeloid-derived suppressor cells, Dr. Radvanyi argues that dendritic cells have not received enough attention. Better understanding how to activate these primary antigen-presenting cells is crucial for priming effective and durable anti-tumor immune responses, especially within tertiary lymphoid structures.

Rather than expecting cell therapies (CAR-T, TIL) to eradicate every cancer cell, Dr. Radvanyi reframes them as powerful adjuvants. Their role is to inflict initial damage, kill tumor cells, and release antigens, creating an opportunity to prime a broader, secondary immune response with other modalities like vaccines or checkpoint inhibitors.

Dr. Radvanyi advocates for a paradigm shift: treating almost all cancers with neoadjuvant immunotherapy immediately after diagnosis. This "kickstarts" an immune response before standard treatments like surgery and chemotherapy, which are known to be immunosuppressive, can weaken the patient's natural defenses against the tumor.

Dr. Radvanyi explains that immune agonist drugs often fail because accelerating a biological pathway is inherently less controllable than inhibiting one. This is analogous to genetic knockouts being more straightforward than over-expression models, presenting a core challenge in drug development beyond just finding the right target.