Abstract
Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7. ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells. Tumor selectivity is mediated by an insulator, a modified E2F promoter, and a Rb-binding site deletion of E1A, whereas replication is optimized with E2F binding hairpins and a Kozak sequence. ICOVIR-7 doses ranged from 2 x 10(10) to 1 x 10(12) viral particles. All patients had advanced and metastatic solid tumors refractory to standard therapies. ICOVIR-7 treatment was well tolerated with mild to moderate fever, fatigue, elevated liver transaminases, chills, and hyponatremia. One patient had grade 3 anemia but no other serious side effects were seen. At baseline, 9 of 21 of patients had neutralizing antibody titers against the ICOVIR-7 capsid. Treatment resulted in neutralizing antibody titer induction within 4 weeks in 16 of 18 patients. No elevations of serum proinflammatory cytokine levels were detected. Viral genomes were detected in the circulation in 18 of 21 of patients after injection and 7 of 15 of the samples were positive 2 to 4 weeks later suggesting viral replication. Overall, objective evidence of antitumor activity was seen in 9 of 17 evaluable patients. In radiological analyses, 5 of 12 evaluable patients had stabilization or reduction in tumor size. These consisted of one partial response, two minor responses and two cases of stable disease, all occurring in patients who had progressive disease before treatment. In summary, ICOVIR-7 treatment is apparently safe, resulting in anticancer activity, and is therefore promising for further clinical testing.
Highlights
MethodsPatients Twenty-one patients with solid tumors refractory to available anticancer modalities were treated with a single round of ICOVIR-7 (Table 1)
Experimental Design: ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells
Oncolytic adenovirus-based therapy represents a novel approach for cancer refractory to conventional therapies [1,2,3], and can be combined with other modalities for synergistic effects [4,5,6,7]
Summary
Patients Twenty-one patients with solid tumors refractory to available anticancer modalities were treated with a single round of ICOVIR-7 (Table 1). All patients had progressive metastatic tumors and signed written informed consent. Symptoms were collected by interviewing the patient at each visit and by collecting their medical records in case they visited other health care providers. Side effects were graded according to CTCAE v3.0. Treatments were done according to Good Clinical Practice and the Helsinki Declaration of the World Medical Association.
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