Duke University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Other

University of Texas System

Secretary, Dhhs

John Howard Sampson

Duane A Mitchell

Darell D Bigner

Matthias Gromeier

Henry S Friedman

Annick Desjardins

Bryan Daehahn Choi

Ira H Pastan

Chien-Tsun Kuan

Michael D Gunn

Kristen A Batich

Mingqing Cai

Patrick C Gedeon

Hai Yan

Bryan Choi

Amy Heimberger

Laura P Hale

Zachary James Reitman

Gary E Archer

David M Ashley

Robert J Schmittling

Allan H Friedman

Bryan D Choi

The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided.

Compositions, methods and kits for eliciting an immune response

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.

Oncolytic poliovirus for human tumors

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

Tetanus toxoid and CCL3 improve DC vaccines

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Sequential treatment with the virus construct followed by chemotherapy drugs increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioblastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

Sequential anti-cancer treatment

We have constructed a polynucleotide encoding a bispecific antibody engaging molecule which has one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The polynucleotide is codon optimized for expression in CHO cells. The subunits of the engaging molecules are organized to achieve greater efficiency. These are therapeutic agents.

Human bispecific EGFRvIII and CD3 antibody engaging molecules

Growing community of inventors

Durham, NC, United States of America

John Howard Sampson