Erik van den Berg highlights a critical paradox in the current standard of care for BK virus infections post-transplant. The only available intervention is lowering immunosuppression to fight the virus, but this simultaneously increases the probability that the patient's immune system will reject the newly transplanted organ.
Related Insights
With highly effective CLL therapies, primary causes of mortality are now infections and secondary cancers from immunodeficiency. Research is now focusing on immune reconstitution after treatment, marking a pivotal shift towards managing long-term survivorship challenges beyond just controlling the leukemia itself.
The drug's mechanism avoids maximum suppression, instead aiming for a precise balance—"not too much, not too little." This "Goldilocks" approach to intercepting BAF and APRIL cytokines is key to resolving inflammation and stabilizing kidney function without causing excessive immunosuppression, a critical differentiator in autoimmune therapies.
A common multiple myeloma treatment, autologous stem cell transplant, causes a significant decrease in beneficial, butyrate-producing gut bacteria. This treatment-induced change is directly associated with inferior progression-free survival, revealing a paradoxical negative effect of a standard therapy.
Despite the individual high efficacy of both BCMA-directed therapies and anti-CD38 antibodies, there is significant clinical concern about combining them. The potential for compounded immunosuppression and severe infection risk is a major barrier shaping clinical trial design and favoring sequential use over concurrent combination.
Memo Therapeutics CEO Erik van den Berg explains the BK virus, dormant in 90% of the population, reactivates under severe immunosuppression required for organ transplants. This doubles the risk of kidney graft failure and triples the risk of death for these patients, who currently have no available treatment.
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.
Modern critical care for sepsis only treats the consequences of the disease—organ failure, low blood pressure—with supportive measures like ventilators and IV fluids. There are zero approved therapies that actually treat the underlying root cause: the out-of-control immune response that is actively damaging the patient's body.
A sophisticated concern regarding the HIF-2 inhibitor belzutifan is its potential to diminish kidney cancer's antigenicity by reducing human endogenous retrovirus expression. While providing an early benefit, this could theoretically make tumors less responsive to subsequent immunotherapies, negatively impacting long-term outcomes—a critical consideration for sequencing.
CLL-associated immunosuppression dramatically increases the risk and aggressiveness of skin cancers. This risk is not mitigated by novel therapies, and in some cases, the secondary skin malignancy can become a greater threat to a patient's life than their underlying CLL.
Bi-specific T-cell engagers (BiTEs) are highly immunogenic because the mechanism activating T-cells to kill cancer also primes them to mount an immune response against the drug itself. This 'collateral effect' is an inherent design challenge for this drug class.
