An Individualized Anti-Cancer Vaccine Study in Patients With HCC

The purpose of this study is to determine the safety and the immunological, radiological, and pathological response of the personalized anti-cancer vaccine AlloVax(TM) in patients with refractory Hepatocellular Carcinoma (HCC) and who are not eligible for any approved HCC treatments or have failed all approved HCC treatments. AlloVax(TM) is a personalized anti-cancer vaccine combining Chaperone Rich Cell Lysate (CRCL) as a source of tumor antigen prepared from patient's tumor and AlloStim(TM) as an adjuvant. The combination of these two components provides a vaccine designed to bring out an immune response capable of finding and killing the tumor cells.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Any Patients with a diagnosis of HCC based on histology or the current accepted radiological measures.
* Age \> 18 years.
* Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment.
* AFP \> 30.
* Patient who is not eligible or failed all approved HCC treatments.

Exclusion Criteria:

* Patient is unable or unwilling to sign informed consent.
* Patients that are participating in other clinical trials evaluating experimental treatments or procedures.
* Severe congestive heart failure (LVEF on echocardiogram \< 20%).
* Severe pulmonary hypertension (By echocardiogram, PAS \>45 mmHg).
* Uncontrolled diabetes mellitus (HBA1C \>9.5%).
* Any autoimmune disorder, which is currently being treated with prednisone or any other immune suppressive medication.
* Patients currently receiving total parenteral nutrition if they have contraindications to oral drugs.
* Patients with positive HIV1, HIV2, HTLV1, HTLV2, and RPR (syphilis).
* Women who are pregnant or breast feeding.
* Patients, based on the opinion of the investigator, should not be enrolled into this study.
* HBV DNA positive.
* If the patient is HBsAg positive or HBcAB positive, but HBV DNA negative, irrespective of his/her anti-HBS status, patient can be enrolled, but will receive preemptive therapy with Lamivudine.
* Patients with HBV DNA positive will not be enroll, but if turned negative with therapy can be enrolled. Patients with HBV and HCV will be followed by HBV DNA and HCV RNA levels during the trial.
* Any metastasis except for portal vein involvement.
* Patients with Child Pugh above B8.
* Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine).
* History of blood transfusion reactions.
* Known allergy to bovine or murine products

• RESULTEpple LM, Bemis LT, Cavanaugh RP, Skope A, Mayer-Sonnenfeld T, Frank C, Olver CS, Lencioni AM, Dusto NL, Tal A, Har-Noy M, Lillehei KO, Katsanis E, Graner MW. Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine. Int J Hyperthermia. 2013 Aug;29(5):390-8. doi: 10.3109/02656736.2013.800997. Epub 2013 Jun 20. PMID 23786302
• RESULTMayer-Sonnenfeld T, Har-Noy M, Lillehei KO, Graner MW. Proteomic analyses of different human tumour-derived chaperone-rich cell lysate (CRCL) anti-cancer vaccines reveal antigen content and strong similarities amongst the vaccines along with a basis for CRCL's unique structure: CRCL vaccine proteome leads to unique structure. Int J Hyperthermia. 2013 Sep;29(6):520-7. doi: 10.3109/02656736.2013.796529. Epub 2013 Jun 4. PMID 23734882
• RESULTLaCasse CJ, Janikashvili N, Larmonier CB, Alizadeh D, Hanke N, Kartchner J, Situ E, Centuori S, Har-Noy M, Bonnotte B, Katsanis E, Larmonier N. Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma-dependent mechanism. J Immunol. 2011 Dec 15;187(12):6310-7. doi: 10.4049/jimmunol.1101812. Epub 2011 Nov 9. PMID 22075702
• RESULTJanikashvili N, LaCasse CJ, Larmonier C, Trad M, Herrell A, Bustamante S, Bonnotte B, Har-Noy M, Larmonier N, Katsanis E. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia. Blood. 2011 Feb 3;117(5):1555-64. doi: 10.1182/blood-2010-06-288621. Epub 2010 Dec 1. PMID 21123824
• RESULTHar-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1. PMID 18834631
• RESULTHar-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.