Evaluation of NBD Peptides as an Adjunct Therapy for the Treatment of Non-Hodgkin

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$420,475.00
Award Year:
2010
Program:
STTR
Phase:
Phase I
Contract:
1R41AI088870-01A1
Award Id:
n/a
Agency Tracking Number:
R41AI088870
Solicitation Year:
2010
Solicitation Topic Code:
NIAID
Solicitation Number:
PA09-081
Small Business Information
P.O.Box 12613, Research Triangle Park, Durham, NC, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
170945617
Principal Investigator:
PATRICK FLOOD
(919) 425-3586
pmflood@intrex.net
Business Contact:
PATRICK FLOOD
(919) 265-3580
pmflood@intrex.net
Research Institution:
University Of Pennsylvania

Office Of Research Services
3451 Walnut Street
PHILADELPHIA, PA, 19104-
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): The NF-?B family of transcription factors plays a central role in the regulation of lymphocyte proliferation, differentiation and survival. Aberrant constitutive activation of NF-?B has been identified in many differentaggressive lymphoid malignancies in humans and contributes to lymphomagenesis and chemotherapeutic resistance by driving the expression of NF-?B target genes that promote cellular proliferation and inhibit cellular apoptosis. Targeted inhibition of NF-?Bactivation represents an attractive strategy for the treatment of lymphoid malignancies. The applicant organization, TheraLogics Inc., has a peptide inhibitor containing an I?B kinase inhibitory sequence NF-?B essential modulator (NEMO) binding domain (NBD). NBD peptide inhibits both IKKa and IKK activity and efficiently blocks classical, NEMO dependent NF-?B activation. In this proposal we will determine whether selective inhibition of the IKK complex in vivo by NBD peptide can safely inhibit aberrant, constitutive NF-?B activity and prolong disease free survival in privately owned dogs with spontaneous, relapsed NHL. NHL is the most common hematopoetic malignancy in the dog, with an annual incidence of ~30/100,000 dogs. Canine NHL shares similar clinical,biological, behavioral, cytogenetic and gene expression characteristics to NHL in humans and significant morbidity and mortality is associated with drug-resistant disease in both species. The purpose of this phase I STTR is to determine whether the use ofNBD peptide as an adjunct agent to cytotoxic chemotherapy is beneficial in the treatment of relapsed NHL in dogs. Our goal is to understand the potential of this agent to enhance apoptotic cell death in malignant lymphocytes and accelerate the translationof an optimized rescue chemotherapeutic strategy into the canine oncology clinics. Furthermore we hypothesize that beneficial effects seen in the canine model will have direct translational relevance to human cancer therapeutics. PUBLIC HEALTH RELEVANCE: The family of NF-?B transcription factors regulates processes involved in lymphocyte proliferation, differentiation and survival. In lymphoma, the pathways that lead to activation of these factors are constitutively active and promote lymphomagenesis and chemotherapy resistance. NEMO-binding domain peptide blocks NF-?B activation and induces cell death in malignant lymphocytes in vitro. The purpose of this phase I STTR is to determine whether the use of NBD peptide as an adjunct agent to chemotherapy is beneficial in the treatment of spontaneous, relapsed NHL in dogs. Our goal is to understand the potential of this agent to enhance apoptotic cell death in malignant lymphocytes and accelerate the translation of an optimized rescue chemotherapeutic strategy into the canine oncology clinics. Furthermore we hypothesize that beneficial effects of NBD peptide seen in the canine model will have direct translational relevance to human cancer therapeutics.

* information listed above is at the time of submission.

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