Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report

Shapira, Michael Y.; Resnick, Igor B.; Bitan, Menachem; Ackerstein, Aliza; Tsirigotis, Panagiotis; Gesundheit, Benjamin; Zilberman, Irena; Miron, Svetlana; Leubovic, A; Slavin, Shimon; Or, Reuven

doi:10.1038/sj.bmt.1705185

Cited by 38 publications

(22 citation statements)

References 21 publications

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“…It is approved for the treatment of psoriasis, 9 and has been studied in patients with steroid resistant/dependent GVHD after HSCT (hematopoietic stem cell transplantation) with some success. 10 Given the dismal responses seen with conventional immunosuppressive treatments for GVHD after transfusion or solid organ transplantation, 1,3 alefacept may offer a reasonable treatment alternative in a setting cwhere outcomes have generally been fatal. Its use may also provide a clinical model for bone marrow failure states.…”

Section: Rapid Resolution Of Gvhd After Orthotopic Liver Transplantatmentioning

confidence: 99%

Rapid resolution of GVHD after orthotopic liver transplantation in a patient treated with alefacept

Stotler¹,

Eghtesad²,

Hsi³

et al. 2009

Blood

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Section: Rapid Resolution Of Gvhd After Orthotopic Liver Transplantatmentioning

confidence: 99%

Rapid resolution of GVHD after orthotopic liver transplantation in a patient treated with alefacept

Stotler¹,

Eghtesad²,

Hsi³

et al. 2009

Blood

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“…Several current studies support alefacept-mediated depletion of CD2 hi T cells in patients during allogeneic hematopoietic stem cell transplant, liver or kidney [22][23][24][25]. All patients developed post-transplant graft-versushost disease (GVHD) but GVHD resolved even after termination of alefacept therapy and patients did not require immunosuppressive drugs [22].…”

Section: Successesmentioning

confidence: 99%

“…These results indicate that high dose alefacept is feasible and safe in heavily transfused patients and depletes both memory T cells and NK cells [22]. Similarly, based on a total response rate of 55% in a phase II trial of BTI-322 (antibody directed to CD2 antigen) for steroid-refractory acute GVHD [41], a standard dose of alefacept (15 mg intramuscular) was used for treatment of seven patients in eight acute GVHD episodes of skin, GI and liver with grade 2-4 [25]. There was an initial rapid response (within days) to alefacept in all patients even those with grade 4 GVHD involving skin (more than 75% body surface area) that was not responding to any prior treatments.…”

Section: Successesmentioning

confidence: 99%

“…Alefacept has not only been used for the treatment of psoriasis but was successfully repurposed for other diseases that involved T cell activation such as type I diabetes (T1D) [20,21], preconditioning in allogeneic hematopoietic stem cell transplantation (HSCT) of pediatric patients with life-threatening nonmalignant diseases [22], kidney and liver transplantation [23][24][25], atopic dermatitis (AD) [26,27],…”

Section: Repurposing Of Alefacept In Different Human Diseases: Succesmentioning

confidence: 99%

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Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

Zaidi¹,

Meng²

2016

Immunother Open Acc

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Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4 + T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cellmediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2 hi memory CD4 + T cells are a significant contributor.

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“…It is the leading cause of nonrelapse mortality in transplant survivors and has a significant impact on their functional status and quality of life. 6 Our group 7 and others 8 have shown that alefacept is active in steroidresistant or steroid-dependent acute GVHD (aGVHD). Considering the relatively low rate of the side effects of alefacept, its efficacy in psoriasis and GVHD, and its effect on T-cell subtypes, we decided to investigate the role of alefacept in a cohort of patients with refractory extensive cGVHD and its possible cellular immunomodulation.…”

Section: Introductionmentioning

confidence: 99%