ALX148 interfering the antibody workup

[Davidwa]

ALX148 study trial is causing serological headache by reacting like warm auto antibody. Is there any way to remove the impacts of ALX148? 

[carolyn swickard]

I haven't even heard of this one - what is it used for?  What disease or what target that is cross-reacting with RBC antigens?

If this is anti-CD47, see the thread on anti-CD47 therapy interference.  Might help, unless this clone is one of the ones mentioned in the last post detailing clones that are not IgG 4. 

 

Edited December 22, 2018 by carolyn swickard

[ap168]

I have a sample from a patient on the ALX-148 version of the anti-CD47. Immucor IgG is not working. Did you end up finding any way to mitigate this?

[carolyn swickard]

I think one of the threads once mentioned Trypsin - maybe check with a reference lab???

[Pony]

I checked the reference from the ALX148 web site and it is bound to an IgG1 frame so the lack of anti-IgG4 in the Immucor -IgG reagents is not going to work.

 

ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile.

Kauder SE¹, Kuo TC¹, Harrabi O¹, Chen A¹, Sangalang E¹, Doyle L¹, Rocha SS¹, Bollini S¹, Han B¹, Sim J¹, Pons J¹, Wan HI¹.

Author information

 

Abstract

CD47 is a widely expressed cell surface protein that functions as an immune checkpoint in cancer. When expressed by tumor cells, CD47 can bind SIRPα on myeloid cells, leading to suppression of tumor cell phagocytosis and other innate immune functions. CD47-SIRPα signaling has also been implicated in the suppression of adaptive antitumor responses, but the relevant cellular functions have yet to be elucidated. Therapeutic blockade of the CD47 pathway may stimulate antitumor immunity and improve cancer therapy. To this end, a novel CD47-blocking molecule, ALX148, was generated by fusing a modified SIRPα D1 domain to an inactive human IgG1 Fc. ALX148 binds CD47 from multiple species with high affinity, inhibits wild type SIRPα binding, and enhances phagocytosis of tumor cells by macrophages. ALX148 has no effect on normal human blood cells in vitro or on blood cell parameters in rodent and non-human primate studies. Across several murine tumor xenograft models, ALX148 enhanced the antitumor activity of different targeted antitumor antibodies. Additionally, ALX148 enhanced the antitumor activity of multiple immunotherapeutic antibodies in syngeneic tumor models. These studies revealed that CD47 blockade with ALX148 induces multiple responses that bridge innate and adaptive immunity. ALX148 stimulates antitumor properties of innate immune cells by promoting dendritic cell activation, macrophage phagocytosis, and a shift of tumor-associated macrophages toward an inflammatory phenotype. ALX148 also stimulated the antitumor properties of adaptive immune cells, causing increased T cell effector function, pro-inflammatory cytokine production, and a reduction in the number of suppressive cells within the tumor microenvironment. Taken together, these results show that ALX148 binds and blocks CD47 with high affinity, induces a broad antitumor immune response, and has a favorable safety profile.