Superallergen-Assisted passive cancer immunotherapy and tertiary lymphoid structures

Superallergen-assisted cancer immunotherapy (SAPCI) is an emerging AllergoOncology approach that harnesses the high-affinity binding properties of superallergens and passive immunoglobulin E (IgE) antibodies to induce targeted anti-tumor inflammation. The SAPCI protocol involves intratumoral administration of human IgE monoclonal antibodies—derived either from atopic donors or produced recombinantly—followed by the localized, controlled introduction of superallergens at the tumor site. This sequence triggers a robust acute inflammatory response, marked by mast cell and basophil degranulation and the release of potent anti-tumor mediators. These mediators orchestrate remodeling of the tumor vasculature, support the development of high endothelial venules, and promote recruitment of naïve T and B lymphocytes—processes essential for the maturation of tertiary lymphoid structures (TLS). Mature TLSs function as intratumoral immune hubs, fostering localized adaptive immune responses and correlating with improved outcomes in diverse solid tumor types. SAPCI faces translational hurdles, including the potential for anaphylaxis from superallergen dissemination and the need to precisely optimize dosing and delivery methods. This review examines the mechanistic basis for SAPCI's ability to promote mature TLS formation in solid tumors, offering a strategy to convert immunologically "cold" tumors into "hot" ones.