The Genevieve Protocol: Phase I/II Evaluation of a Dual Targeted Approach to Cancer Gene Therapy/ Immunotherapy

Jorge Ignacio G, Filomena San Juan, Roseo Manalo A, Elham Soheili Nategh, Jaee Tamhane, Leela Kantamneni, Sant Chawla P, Frederick Hall L and Erlinda Gordon M

Philippine General Hospital, Manila, Philippines
University of the Philippines, Manila, Philippines
Asian Hospital and Medical Center, Ayala Alabang, Philippines
Cancer Center of Southern California, Santa Monica CA, USA
Delta Next-Gen, LLC, USA
Aveni Foundation, Santa Monica CA, USA

^*Correspondance to: Erlinda M. Gordon 

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Abstract:

A Phase I/II study using two tumor-targeted retro vectors (Rexin-G, encoding a cytocidal dominant negative human cyclin G1 construct, and Reximmune-C, encoding a GM-CSF gene), was conducted in chemoresistant solid malignancies and B-cell lymphoma.Patients and
Methods: Sixteen patients received Rexin-G (2 x 10e11 cfu, i.v. on D1, D3, and D5 and escalating doses of Reximmune-C (0.5 x 10e10 cfu to 2.0 x 10e10 cfu i.v.) on D3 and valacyclovir (3 gms/day p.o.) on D6-D19.Results: No dose-limiting toxicity was observed. Post- treatment, GM-CSF serum levels were normal, and no vector neutralizing antibodies, RCR or vector integration in PBLs was detected. At Dose I, 2/5 patients had PR; 1/5 patients, SD, 2/5, PD; median PFS was 4.5 months, median OS, 21 months, one-year OS rate, 80%. At Dose II, 1/4 patients had PR, 3/4 patients, SD; median PFS was 9 months, median OS, 13 months, one-year OS rate, 50%. At Dose III, 2/7 patients had PR, 5/7 patients, SD; median PFS was 13 months, median OS, >21 months, one-year OS rate, 86%. Taken together, these data suggest that the Genevieve protocol is safe, may control tumor growth, and may prolong progression-free and overall survival in patients with chemoresistant solid malignancies and B-cell lymphoma.

Keywords:

Targeted gene delivery; Cancer immunotherapy; Cell cycle control; Gene therapy

Cite the Article:

Jorge Ignacio G, San Juan F, Roseo Manalo A, Soheili Nategh E, Tamhane J, Kantamneni L, et al. The Genevieve Protocol: Phase I/II Evaluation of a Dual Targeted Approach to Cancer Gene Therapy/Immunotherapy. Clin Oncol. 2018; 3: 1537.