In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer

Phase I Feasibility Study of ALLOSTIM(TM) in Combination With Radiofrequency Ablation in Patients With Refractory Hepatocellular Carcinoma

This study is an individualized anti-cancer vaccine protocol where the vaccination occurs inside of the body. To create the vaccine, a tumor lesion is selected and caused to die by a process called "Radiofrequency Ablation" or RFA. RFA causes the tumor to release its internal contents to the surrounding environment, such contents include tumor-specific antigens. Immune cells respond to the tissue damage and take-up these tumor antigens. The injection of the experimental cell drug, AlloStim(TM) into the lesion is designed to cause the responding cells to signal the immune system of the danger of the tumor, creating tumor-specific immunity.

The protocol design has 4 steps: (1) priming; (2) vaccination, (3) activation and (4) boosting. The priming step involves intradermal injections of AlloStim(TM). This is designed to increase the circulating titer of allo-specific Th1 memory cells; the vaccination step involves percutaneous radiofrequency ablation of a single liver lesion followed immediately with an intratumoral injection of AlloStim(TM) into the ablated lesion, followed 3 days later by an additional intratumoral injection into the previously ablated lesion with AlloStim(TM). This step is designed to elicit tumor-specific Th1 immunity. The activation step involves intravenous infusions of AlloStim(TM). This step is designed to cause the activation and extravasation of circulating memory cells and the activation of innate immune cells. The booster step includes two monthly IV infusions of AlloStim(TM). This step is designed to maintain an inflammatory cytokine storm designed to counteract immune suppressor mechanisms and tumor immunoavoidance mechanisms.

Inclusion Criteria:

1. Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures.
2. Age > 18 years.
3. Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment.
4. AFP >30.
5. Patient who is not eligible for or failed any HCC treatment.

Exclusion Criteria:

1. Patient is unable or unwilling to sign informed consent.
2. Patients that are participating in other clinical trials evaluating experimental treatments or procedures
3. Severe congestive heart failure (LVEF on echocardiogram < 20%).
4. Severe pulmonary hypertension (By echocardiogram, PAS >45 mmHg).
5. Uncontrolled diabetes mellitus (HBA1C >9.5%).
6. Any autoimmune disorder, which is currently being treated with prednisone or any other immune suppressive medication.
7. Patients currently receiving total parenteral nutrition if they have contraindications to oral drugs.
8. Subjects with positive HIV.
9. Women who are pregnant or breast feeding.
10. Patient, based on the opinion of the investigator, should not be enrolled into this study.
11. HBsAg positive or HBV DNA positive.
12. If the patient is HBcAB positive but HBsAG negative, irrespective of his anti HBS status, he can be enrolled but will receive preemptive therapy with Lamivudine.
13. Any metastasis except for portal vein involvement.
14. Subjects with Child Pugh above B8.
15. Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine).
16. History of blood transfusion reactions.
17. Known allergy to bovine or murine products