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Preprint WatchMildJuly 8th, 2026

CD47 blockade augments anti-GD2 driven phagocytosis in vitro but fails to improve in vivo efficacy in immune competent, chemoresistant neuroblastoma preclinical models

Himsworth, C.; Jackson, T.; Bowers, C.; Munnings-Tomes, S.; Nair, G.; Muller, H.; Tucker, E.; Erbe-Gurel, A. K.; Sondel, P.; Chesler, L.; Mazjner, R.; Anderson, J.

A Fc-silent CD47 blocker (ALX301) augments anti-GD2 driven macrophage phagocytosis in vitro but fails to improve tumor control or survival in vivo in immune-competent, chemoresistant neuroblastoma models.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

The preprint reports that a Fc-silent CD47 blocker augmented anti-GD2 phagocytosis in macrophage coculture but failed to improve tumor control or survival in two immune-competent, chemoresistant neuroblastoma models, and the authors conclude that CD47 inhibition alone is insufficient without myeloid-reprogramming partners. That in vitro to in vivo gap aligns with the indexed CD47 failure on file, the discontinued Phase 2 magrolimab program in classic Hodgkin lymphoma (magrolimab-cd47-classic-hodgkin-lymphoma-phase2-program-discontinuation), which ended as a sponsor decision. Both records point to the same recurring pattern for CD47 blockade, where mechanistic phagocytosis signals have not translated into durable clinical efficacy.

Abstract excerpt

CD47 delivers a dominant "Dont Eat Me" signal that inhibits macrophage-mediated clearance of tumour cells. Using immune competent, chemoresistant neuroblastoma (NB) models, we tested a Fc-silent CD47 blocker (ALX301) with anti-GD2 antibody alone and in combination with a clinically aligned temozolomide/irinotecan chemoimmunotherapy backbone. Tumours expressed GD2 and CD47, and bound ALX301. In macrophage coculture assays, anti-GD2 antibody induced dose-dependent phagocytosis, whereas ALX301 or an anti-CD47 antibody alone did not. CD47 blockade in combination with a suboptimal concentration of anti-GD2 antibody showed an additive effect on phagocytosis in vitro. In vivo, however, ALX301 failed to improve tumour control or survival when added to anti-GD2 or to chemoimmunotherapy in two models. Toxicity was acceptable, showing only mild, expected red-cell changes without organ injury. This form of CD47 inhibition is therefore mechanistically active in vitro but insufficient to enhance anti-GD2 antibody-based therapy in immune competent mice bearing a chemoresistant NB, highlighting the potential need for myeloid-reprogramming partners.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.