MEDICAL HYPOTHESES AND RESEARCH
VOL. 4, No. 2, July 2008




M. Har-Noy, et al. [2008] Med. Hypotheses Res. 2: 85‒91.


Immunotherapy for Invasive Aspergillosis in
Immunocompromised Post-Engraftment Allogeneic
Bone Marrow Transplant Patients



M. Har-Noy*, L. Weiss1, E. Sioonov, I. Polacheck and R. Or

Hadassah-Hebrew University Medical Center, Department of Bone Marrow Transplant and
Cancer Immunotherapy; Department of Clinical Microbiology and Infectious Diseases,
Jerusalem, Israel 91120; and Immunovative Therapies, Ltd., POB 974, Shoham, Israel 60850.


Abstract. Invasive aspergillosis (IA) is a dangerous infection that is common in
immunocompromised patients.  IA is a major cause of mortality in bone marrow transplant
(BMT) patients due to steroid-induced immunosuppression and chemotherapy-induced
neutropenia. In normal individuals, Aspergillus is controlled by a Type 1 immune response.
However, immunocompromised patients have a decreased ability to mount a Type 1 immune
response. BMT patients are treated with glucocorticoids to suppress the Type 1 immune
response which is associated with graft versus host disease (GVHD) toxicity. Therefore it is a
complex problem to develop strategies to enhance Type 1 immunity without also causing
GVHD. To overcome this problem, we propose that multiple intradermal injections of
activated allogeneic Th1 memory cells will create a pool of alloantigen-specific Th1 memory
cells in the circulation. Intradermal allogeneic injections are expected to be rejected and thus
not cause GVHD. Additional intradermal allogeneic Th1 cell injections should activate the
anti-alloantigen memory cells in circulation causing them to migrate to the sites of fungal
infection and produce Type 1 cytokines. This Type 1 cytokine production in the
microenvironment of the fungal infection should serve as an adjuvant to the stimulation of
innate immune responses against the fungus and the development of Type 1 anti-fungal
adaptive immunity.  


Correspondence: Dr. M. Har-Noy, Hadassah-Hebrew University Medical Center,
Department of Bone Marrow Transplant and Cancer Immunotherapy, P.O. Box 12000,
Jerusalem, Israel 91120.




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