Abstracts for the 25th Annual Scientific Meeting of the International ...

Abstracts J Immunother Volume 33, Number 8, October 2010
immune response eliminate everywhere, the patient’s body, the
recognised none histocompatible cancer cells through his unique
selectivity, detection-ability intelligence.
We present a rare case of a 70 year old man with primary renal
adenacarcinoma. The first diagnosis was fifteen years ago and was
followed by right nefrectomy. The follow-up study was discovered
a remission in the left kidney three years later. The patient was
undertaken in a partial left nefrectomy but one year later a new one
mass in the left renal remnant was revealed by follow up research
study and a complete bilateral nefrectomy was the final surgical
curative result. Because of the renal failure he was under
haemodialysis the last 11 years. Chemotherapy by antiangiogenetic
regimen was followed because of liver secondaries without
improvement. Two years ago applied in a 2-cycle simulation
AHICE-therapy with successful results and remission of liver
secondaries. The patient died, 10 months ago, suddenly, during his
gardening usual activities from a heart infarct.
In conclusion we address the effectiveness of impulse AHICE-therapy
in a rare, difficult and immunocompromised case of an elderly man.
Autologous Human Vaccine, AHICE, for Multi-Primary
Cancer Therapy
Konstantinos I. Papapolychroniadis*, Hannes Anthopoulosw,
Aristidis Ioannidis*, Epaminondas Fahantidis*, Julia
Papapolychroniadou*, Mairi D. Georgiou*. *1st Surgical Propedeutical,
Aristotle University of Thessaloniki, Thessaloniki, Greece;
w Cell biotechnology and immunology, Clinical Biochemical Institute,
Munich, Germany.
The Autologous Human Immune Vaccine AHICE therapy is of
high specificity against tumour- and their metastatic cells. Their
autologous production is initiated on at a specific biochemical
treatment (patent). This means, that patient’s own immune-system
will get the specific information of the altered shape of the target-,
cancer- cells and is thereafter able to identify them as none healthy
body-cells. After that, the immune-system begins to kill the so
identified target cells via antigen-specific activation of the natural
killer cells (NKC). This is highly specific, but very complexed
immunological/biochemical mechanism. Thereafter, it is the greatest
benefit, that patient’s own immune-system can so identify and
eliminate the altered target cells, not only in the primary tumour
site, but also the metastatic regions everywhere in the whole
patient’s body (‘‘intelligent phenomenon’’). In this consecutive case
series study we report the therapy principles and results of thirty
(30) multi-primary cancer patients. In five cases a second one
AHICE cycle was followed. The period of each one therapy cycle
was 90 days. No one patient had side effects or complications. Two
patients presented an ischemic brain attack and ascites, without any
relation to vaccine therapy.In conclusion, analysis of our present
study results refers that lymphocytes are the most important immune
component for active immune anticancer management. AHICE
therapy is well tolerated, effective, uncomplicated plus good quality
of life and survival anticancer optional therapy. We need more cases
for randomised trials in the near future.
Adoptive Immunotherapy for Recurrent Ovarian Cancer
Using Autologous Whole Tumor Antigen-Primed T Lymphocytes
Daniel J. Powell*w, Lana Kandalaft*, Lori Smith*, John Liao*,
Andrea Hageman*, Janos Tanyi*, Qunrui Ye*, Andrew Best*,
Drew A. Torigianw, Christina S. Chu*, Stephen C. Rubin*,
Edward Stadtmauerw, Marnix Boschz, Bruce L. Levinew, Carl H.
Junew, George Coukos*. Departments of *Obstetrics and Gynecology;
w Pathology and Laboratory Medicine, University of Pennsylvania,
Philadelphia, PA; zNW Biotherapeutics, Inc., Bethesda, MD.
Background: Novel therapeutic strategies are warranted in recurrent
ovarian cancer. We report the pilot application of combinatorial
immunotherapy comprising dendritic cell (DC)-based
autologous whole tumor antigen vaccination in combination with
antiangiogenesis therapy, followed by adoptive transfer of autologous
vaccine-primed CD3/CD28-costimulated lymphocytes in
patients with recurrent ovarian cancer.
Methods: Patients with recurrent progressive stage III and IV
ovarian cancer underwent priming with intravenous bevacizumab
and oral metronomic cyclophosphamide, followed by vaccination
with DCVax-L, an autologous DC preparation pulsed with
autologous tumor lysate, plus bevacizumab. This was followed by
lymphodepletion using high-dose outpatient cyclophosphamide
and fludarabine (cy/flu) and transfer of autologous vaccine-primed,
ex vivo CD3/CD28-costimulated peripheral blood T cells, in
combination with DCVax-L vaccination.
Results: Six subjects received vaccination alone; three subsequently
completed T cell transfer therapy. Vaccination with DCVax-L
following bev/cy produced few grade 1 toxicities and elicited
tumor-specific T cell and humoral responses. Partial objective
response was observed in two patients after completion of vaccine;
two additional patients demonstrated stable disease. Among the
former, one subject progressed through bev/cy, but had objective
response to DCVax-L. Three vaccine recipients with detectable
vaccine priming subsequently received adoptive transfer of vaccineprimed,
CD3/CD28-costimulated autologous T cells following
outpatient cy/flu lymphodepletion. One patient, who exhibited no
evidence of disease at end of study, experienced a durable reduction
of CD4+FOXP3+ T regulatory cells, increased total lymphocyte
counts and restoration of vaccine-induced antitumor immunity.
Stable disease was observed in a second subject. In the third
subject, adoptive immunotherapy was not followed by restoration
of vaccine-induced antitumor immunity and disease progression
was observed. Updates will be presented at the meeting.
Interpretation: The use of combinatorial cellular immunotherapy
comprising bev/cy with DC vaccination with whole tumor antigen
and adoptive immunotherapy using tumor antigen-primed T cells
for the treatment of patients with recurrent ovarian cancer
warrants further investigation.
T Cell Activation, PSMA Seroconversion and Increased
Th17 Rates are Associated with Favorable Clinical Outcome
in Prostate Cancer Patients Treated with Prostate GVAX
and Anti-CTLA4 Immunotherapy
Saskia J. Santegoets*, Alfons J. van den Eertwegh*, Anita G.
Stamw, Rik J. Scheperw, Sinead M. Lougheed*, Petra E. Scholtenw,
Mary von Blombergw, Helen Gall*, Karin Joossz, Nathalie Sacksz,
Tom Hardingz, Kristen Hegez, Israel Lowyy, Winald
R. Gerritsen*, Tanja D. de Gruijl*. *Medical Oncology; w Pathology,
VU University Medical center, Amsterdam, Netherlands; zCell
Genesys, South San Fransisco, CA; yMedarex, Bloomsbury, NJ.
The effects of Prostate GVAX and the anti-CTLA4 antibody
Ipilimumab were investigated in a Phase I dose escalation/expansion
trial of patients with prostate cancer. Results showed that the
GVAX/Ipilimumab combination was clinically active with PSA
declines of more than 50% (Partial Response, PR) in 5 of 22
patients and PSA stabilizations (Stable Disease, SD) in 7 of 22
patients in the higher (3 to 5 mg/kg) Ipilimumab dose levels.
Immune response monitoring was performed to identify changes
that might predict or correlate with clinical efficacy. Most notably,
pronounced and significant increases in frequencies of activated
CD4+ and CD8+ T cells were observed by HLA-DR and ICOS
expression upon administration of high (3-5 mg/kg) but not of low
(0.3 to 1 mg/kg) Ipilimumab dosages. Of these, only early HLA-DR
up-regulation might be useful as a marker for response prediction,
since it was observed to significant levels in PR or SD, but not in PD
patients. As an indication of tumor-specific responsiveness we tested
NY-ESO-1 and PSMA specific seroreactivity and HLA-Tetramer
(Tm) binding. For NY-ESO-1, GVAX/Ipilimumab-induced increased
seroreactivity was observed in 6/28 patients. In 2 of 3 of these
patients, increased NY-ESO157 T cell rates were also found,
whereas no Tm reactivity was detected in 8 patients without
NY-ESO-1 seroreactivity. Interestingly, PSMA seroconversions
were observed in a total of 12/28 patients and were found to
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