Immunomodulators

8:30 - 8:35 Chairperson's Remarks

KEYNOTE PRESENTATION:

8:35 - 9:05  Targeting Toll-Like Receptor 9 for Cancer Therapy Arthur M. Krieg, M.D., Founder & Chief Scientific Officer, Coley Pharmaceutical Group Inc., USA Toll-like receptors (TLRs) are a family of immune defense proteins that appear to have evolved to detect molecules that are present in general classes of pathogens, but are not present in our own cells. Toll-like receptor 9 (TLR9) detects "CpG motifs" in pathogen DNA, and can be activated for therapeutic purposes by a synthetic oligodeoxynucleotide, PF-3512676, which can stimulate innate and adaptive immunity against tumors. Based on positive results with PF-3512676 as a single agent in several human tumors, and in combination with standard chemotherapy for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), two phase III human trials of this drug have been initiated in NSCLC.

9:05 - 9:35 Exploit Inflammation to Induce Anti-Tumor Immunity: Old Weapons and New Effector Mechanisms
Sven Brandau, Ph.D., Head, Division of Immunotherapy, Department of Immunology and Cell Biology, Research Center Borstel, Germany
Researchers have realized for a long time the power of mycobacterial antigens in enhancing anti-tumor immune responses but the cellular mechanisms and how to rationally exploit them have remained largely elusive. Only recently we and others have more precisely defined the molecular interaction of mycobacteria and mycobacterial antigens with anti-tumor effector cells. Also, defined recombinant antigens and genetically engineered mycobacteria open the door for more precisely designed therapies. The identification of novel molecular and cellular interactions between bacterial antigens and cells of the innate immune system sheds new light on the use of these biologic response modifiers in cancer immunotherapy.

Dendritic Cells

9:35 - 10:05 A Novel Anti-Tumor DC Immunotherapy with Greatly Improved Immunopotency
Charles Nicolette, Ph.D., Vice President, R&D, Argos Therapeutics, Inc., USA
The clinical efficacy of DC-based immunotherapies has thus far been disappointing. We have developed an autologous immunotherapy based on DCs loaded with amplified total tumor RNA. Combined with a newly developed DC maturation method, high avidity anti-tumor CTL can be generated in vitro even when tumor epitopes are presented in vanishingly small quantities. Furthermore, these DCs are capable of continually inducing CTL proliferation upon repeated stimulation and are therefore ideally suited to long-term boosting strategies in vivo. In contrast to other approaches, the proposed immunotherapeutic product platform is adaptable to any tumor indication regardless of the patient's MHC haplotype and is perfectly matched to each patient's unique tumor immunome. Additionally, since only a minute tumor specimen is required to manufacture several years worth of doses, very early stage patients can be addressed. A clinical trial treating RCC patients has been recently initiated.

10:05 - 10:45 Coffee Break in the Exhibit Hall 

10:45 - 11:15 Phase I Clinical Data of Dendritic Cell Immunotherapy of Brain Cancer
Alton Boynton, Ph.D., President, Northwest Biotherapeutics, USA
Newly diagnosed patients with glioblastoma following standard of care progress in 7-8 months and only live 14-15 months. Our phase I data using autologous dendritic cells loaded with autologous tumor lysate shows patients with median time to progression to date of 15 months (median not yet reached) and median survival to date of 21 months (median not yet reached). 8 of 10 patients are still alive and 5 of 10 have not progressed.

Novel Vaccines

11:15 - 11:30 Listeria-Based Immunotherapy: Cancer Vaccines Disguised as Invading Pathogens
Dr. Dirk Brockstedt, Director, Immunology, Cerus Corporation
The considerable progress in understanding molecular and cellular pathways of innate and adaptive immune cell activation as well as host-pathogen interactions have built the foundation for the development of vaccines for tumor-targeted immunotherapy. The intracellular bacterium Listeria monocytogenes (Lm) is known for its ability to induce potent innate and adaptive CD4+/CD8+ cellular immunity that correlates with therapeutic anti-tumor efficacy in syngeneic tumor models. We describe development of a clinical vaccine strain, known as CRS-100, that segregates the profound immunostimulatory properties of Lm from its toxicity. The presentation will cover recent preclinical advances to utilize this strain to develop an immunotherapy for pancreas and ovarian cancer, and description of a planned Phase I safety trial with CRS-100 in adult human subjects with carcinoma and liver metastases. 

11:30-11:45 Technology Trends (Sponsorship Available)

11:45 - 12:15 Tumor Therapy by Polyclonal T Cell Activation
Patrick A. Baeuerle, Ph.D., CSO, R&D, Micromet AG, Germany
Preclinical and clinical data with MT103, a single-chain bispecific antibody construct of the BiTE(TM) class with specificity for CD19 and CD3, will be presented. Partial and complete tumor responses in therapy-refractory Non-Hodgkin lymphoma patients are being observed with MT103 doses as low as 30 microgram/patient and day. These very recent data show for the first time that BiTE therapeutics work in man.

12:15 - 1:40 Luncheon Technology Workshop or Lunch on Your Own  (Sponsorship Available) 

1:40 - 1:45 Chairperson's Remarks

1:45 - 2:15 A Peptide Vaccine Targeting EGFRvIII Shows Efficacy in Phase I and II Trials for Glioblastoma
Albert Wong, M.D., Professor, Department of Cancer Biology/Neurosurgery, Stanford UniversityMedical Center, USA
EGFRvIII is a naturally occurring splice variant of the EGF receptor that is highly expressed inglioblastoma and can also be found in many other tumors, but not normal tissues. For thesereasons, it is an ideal tumor specific epitope. Animal models have shown that vaccinationwith a peptide derived from the EGFRvIII fusion can both prevent tumor formation andinduce regression of existing tumors. Both a CTL and antibody response can be found in vac-cinated animals. A Phase I trial has shown a near tripling in time to progression and a dou-bling in survival. An ongoing Phase II trial has shown a statistically significant (P=0.0058) dif-ference in time to progression.

2:15 - 2:45 A Fully Synthetic Three-Component Cancer Vaccine 
Geert-Jan Boons, Ph.D., Complex Carbohydrate Research Center, The University of Georgia, USA
A common feature of oncogenic transformed cells is the over-expression of complex carbohydrates such as Globo-H, LewisY and Tn antigens. Numerous studies have shown that this abnormal glycosylation can promote metastasis and hence its expression is strongly correlated with poor survival rates of cancer patients. Efforts to exploit the differential expression of tumor-associated carbohydrates for the development of cancer vaccines are complicated by the poor immunogenicity of these compounds. We have addressed this problem by the chemical synthesis and immunological evaluation of a fully synthetic anti-cancer vaccine candidate that is composed of a tumor-associated carbohydrate B-epitope, promiscuous peptide T-cell epitope, and the in-built immune adjuvant Pam3CysSK4, which is a ligand for Toll Like Receptor-2 (TLR-2). 

2:45 - 3:15 Trovax: A Novel Cancer Vaccine for the Treatment of Renal Cancer
Robert Amato, M.D., Genitourinary Oncology Center, The Methodist Hospital, USA
TroVax is a cancer vaccine consisting of an attenuated Vaccinia virus vector (MVA) encodinga tumour antigen 5T4 that is expressed at high levels on the majority of solid tumours includ-ing colorectal, renal and prostate cancer. A number of Phase I/II clinical studies have beencompleted that indicate TroVax is safe and extremely well tolerated. In addition the majorityof patients elicit both a cellular and humoral immune response to the 5T4 tumour antigen. Ofparticular note is that in two of the studies an association has been identified between theimmune response elicited by TroVax and indications of clinical benefit. We have recently ini-tiated Phase II studies in renal cancer, a tumour that expressed very high levels of 5T4. Datafrom these studies confirm safety and early indications suggest significant tumour responses.TroVax appears to be a compelling cancer vaccine candidate and the data suggest progres-sion to larger randomised study.

3:15 - 4:00 Refreshment Break in the Exhibit Hall 

4:00 - 4:30 Uing Monoclonal Antibodies to Induce Tumor Specific Immunity
Christopher Nicodemus, M.D., Senior Vice President, Research and Development, UnitherPharmaceuticals, USA
Cancer patients are generally immune non-reponsive to their associated tumor antigens andtumors. Multiple pathways that counter regulate specific immunity have been implicated. Wehave been studying the use of high affinity xenotypic monoclonal antibodies targeting circu-lating tumor antigens to alter antigen processing and induce robust CD4 and CD8 antigenspecific cellular immunity. Preclinical and clinical data demonstrating both the pathway andthe clinical application in ovarian cancer will be presented.

4:30 - 5:00 The Anti-Tumor Potency of The HUC242-DM4, an Antibody Drug Conjugate in Clinical Testing, is Enhanced by Linker-DependentBystander Killing
Hans Erickson, Ph.D., Scientist, Department of Biochemistry, Immunogen, USA
We have developed maytansinoid conjugates of the humanized monoclonal antibody,huC242, which binds to the CanAg antigen expressed on colorectal, pancreatic, and certainnon-small cell lung cancers. One conjugate, huC242-DM4 displayed superior preclinicalactivity and is currently being evaluated in a phase 1 clinical trial. We employed both biolog-ical and biochemical methods to investigate the mechanism for the enhanced anti-tumoractivity of huC242-DM4 over similar conjugates that differ only in the chemical nature of thelinker between the maytanisnoid and the antibody. Our findings provide insight into themechanism of action of antibody-maytansinoid conjugates in general, and more specifically,identify a biochemical mechanism that may account for the significantly enhanced anti-tumorefficacy observed with disulfide-linked conjugates.

5:00 End of Conference