Duke University

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

Vidyalakshmi Chandramohan

Darell D Bigner

Matthias Gromeier

Smita K Nair

Ira H Pastan

Charles Pegram

Xuhui Bao

Smita Nair

A reliable assay to specifically detect CD155 in tissue sections has widespread use because CD155 is expressed widely among tumor types. Additionally, detected expression of CD 155 in glioblastoma cells is at levels commensurate with susceptibility to PVSRIPO (a poliovirus construct) infection and killing. An anti-CD155 antibody can achieve mono-specific detection of CD155 in immunoblots of tumor homogenates and immunohistochemistry of tumor formalin fixed, paraffin embedded sections. The assay can be used to determine appropriate use of PVSRIPO in oncolytic immunotherapy against cancers.

Detection of CD-155, the poliovirus receptor

D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a recombinantexotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a Phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter inBLR (&#x3bb; DE31). D2C7-IT was produced by a 10 L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein.

Production of immunotoxin D2C7&#x2014;(scdsFv)&#x2014;PE38KDEL

Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

Combination therapy of immunotoxin and checkpoint inhibitor

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

Growing community of inventors

Durham, NC, United States of America

Vidyalakshmi Chandramohan