Day 3 :
- 21 Immunotherapy Monitoring
18 Cancer biomarkers
23 Engineered T-cell Therapy
24 Novel Approches
Location: Melbourne, Australia
Session Introduction
Hsu-Shan Huang
Taipei Medical University, Taiwan
Title: Drug development for EGFR-TKI resistance in non-small cell lung cancer cells: novel dual inhibitor of EGFR and cMET
Time : 10:00-10:25
Biography:
Hsu-Shan Huang has completed his Dr. rer. nat. at the age of 34 years from Regensburg University, Germany and pharmaceutical studies from NDMC School of Pharmacy. He was the dean of School of Pharmacy and director of R&D, NDMC. He has published more than 95 SCI papers and 30 patents in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15% globally, accounting for more than 1.4 million deaths per year. Lung cancer is one of the most heavily mutated and genomically altered cancers. Despite the longer progression free survival of patients with TKI-treatment a high proportion eventually develop resistance. Resistance to targeted therapies is generally classified as either primary (i.e. intrinsic) or secondary (i.e. acquired). This approach has been variously termed “personalized cancer medicineâ€, “individualized cancer medicine†or “high precision cancer medicineâ€. Chemical synthesis led to further compound evaluations that revealed increased biochemical potency. The earliest efforts to utilize molecular profiling of tumors to guide more precise therapies for individual patients have met with remarkable success. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that NSC777201 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin-proteasomes. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKItargeting therapies.
Roberta Mazzieri
The University of Queensland Diamantina Institute, Australia
Title: Tumour associated Tie2+ macrophages: novel targets and effectors of anti-breast cancer therapies
Time : 10:25-10:50
Biography:
Dr Roberta Mazzieri obtained her PhD in Genetic Science from the University of Pavia (Italy) and subsequently undertook one post-doctoral position at the New York University (USA) and two at the San Raffaele Scientific Institute in Milan (Italy). In 2012 she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications. The same year she was recruited by the University of Queensland (Brisbane) to establish her own research group to continue her work on targeting pro-tumoural macrophages.
Abstract:
While advances in treatment and screening have greatly improved outcomes for most breast cancer patients, major unmet needs remain for treatment of patients with metastatic disease. Breast cancer has not benefitted to the same extent as other cancers from the recent introduction of immunotherapies due to poor inherent immunogenicity of breast tumours associated with a highly immunosuppressive microenvironment. New strategies are needed to overcome these limitations. We identified and characterized a subpopulation of pro-tumoural macrophages: the Tie2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogenic and immunosuppressive activities, both involving signalling through the ANG2/TIE2 pathway. Indeed we demonstrated that blocking the ANG2/TIE2 pathway disables the pro-angiogenic activity of TEMs resulting in inhibition of tumour angiogenesis, growth, and metastasis in mouse models of breast carcinogenesis. We are now investigating whether the in vivo blockade of ANG2 is not only inhibiting the pro-angiogenic activity of TEMs, but also reverting their immunosuppressive activity, thus providing a strong rational for the development and testing of new combination therapies. Moreover, by exploiting the tumor homing ability of TEMs we turned them into an efficient vehicle for the tumor-targeted delivery of a potent immune-stimulatory molecule: interferon-alphaï€ ï€¨IFNα. We think that the multiple activities of type I IFNs in the complex network of cell interactions that lead to activation and deployment of immune responses may represent a valid strategy to promote and improve the outcome of cancer immunotherapy for the treatment of advanced breast cancer including lung and bone metastasis.
George Kunuji
Bikbok Herbal Centre, Ghana
Title: Efficacy of Immune pressure on the progression of tumor and its escape
Time : 11:35-12:00
Biography:
Dr. George Kunuji attained his PhD from the University of Ghana, Legon and postdoctoral studies from University of Ghana Medical School. He is the director of Bikbok Herbal Centre, a reputable herbal organisation that is dispensing services across the country, Ghana and currently discovered herbal antidote to the treatment of cancer tumor. Moreover, he have been serving as the chairman of the health advocacy group of Asuboa Traditional Council and Nifahene(Nifa chief) of Asuboa Traditional Area.
Abstract:
Although cancers develop and being progress in immunocompetent hosts, immunological therapies for cancer have been proposed as an major alternative or complementary approaches to more standard therapy. It was initially thought to be that tumours were silent to the immune system, and that breaking immunological tolerance could result in immune-mediated tumour rejection. Attempts to develop combinatorial therapies by depleting suppressor cells or blocking suppressor pathways and at the same time actively inducing immune responses in vivo or adoptively transferring tumour-specific T cells have largely failed. Genomic testing is a rapidly developing area of medical science, there are currently only a few cancers where such testing is considered to be routine in the evaluation of possible treatment options. An overview reveals that the diagnoses of 3000 consecutively accessioned oral biopsies from the Oral Pathology. Depleted success has been achieved only against melanoma, using adoptive T-cell therapy, or prostate cancer, using a vaccine which improves patient survival but has no possible effective inhibitory effect on disease progression. This special issue is focused on understanding the escape mechanisms that malignant cells develop to destroy antitumor immune responses as well as strategies to overcome tumour escape. This drastic issue addresses many areas and one that can be talked of is the opposing function of the immune system in tumour inhibition and tumour progression. In that “cancer immune editing” describes the dual host-protecting and tumours-sculpting actions of the immune system that not only survey for, and elimininate, nascent malignant cells but also shape neoplastic disease through equilibrium and escape mechanisms. Many areas could further be elaborated on herbs and cancer tumour.
Biography:
Alex Agyekum has attained his PhD from the University of Ghana, Legon and Postdoctoral studies from University of Ghana Medical School. He is the Diagnostic Radiologist of Bikbok Herbal Centre, a reputable herbal organization that is dispensing services across the country, Ghana and currently discovered herbal antidote to the treatment of cancer tumor.
Abstract:
Diagnostic testing involves of specific disease tests and procedures to confirm the presence of disease and identify the correct tumour type, location, extent and stage. Our Herbal centre diagnostic team includes physicians across many medical specialties, including radiologists, pathologists and geneticists. However treatment is herbal base which is so effective and newly immerging in Ghana. A thorough and accurate cancer diagnosis is the eventually important first step in developing & Improving an individualized cancer treatment plan. A diagnostic plan test varies as follows: A preview of health history, Physical examination, Laboratory tests (blood, urine, etc.), Biopsy, Imaging tests (X-ray, PET/CT, MRI, ultrasound, etc.), Nuclear medicine scans (bone scans, etc.), Endoscopy and Genetic tests. Before treatment, we will accurately identified & locate tumours, stage the disease, and determine an appropriate combination of cancer treatments for you. Tumour molecular profiling helps us identify the right chemotherapy or targeted therapy Endoscopic ultrasound allows us to find and reach very small tumours without the risks of surgery. Genomic testing: BIKBOK Herbal Centre offers expanded genomic tumour assessment. This tool reveals the DNA alterations that are driving the growth of a cancer. All odontogenic neoplasm, neoplasm-like lesions (tumours), and true cysts of the oral tissues and jaws were listed. Of a total of 445 (1.11%) odontogenic tumours, 392 (0.98%) were lesions from patients in the usual local drawing area of the biopsy service; 53 were referred from distant centres. From the local population, odontomas were by far the most common tumour (51.53%) followed by ameloblastomas (13.52%) and peripheral odontogenic fibromas (8.93%). Locally, radicular (periapical) cysts were the most common odontogenic cyst (65.15%) followed by the dentigerous cyst (24.08%) and the odontogenic keratocyst (4.88%). The most common nonodontogenic cyst was the nasopalatine duct cyst that accounted for 73.43% of this subset of cysts. Surprisingly few studies of this type are available, especially for odontogenic tumours. The given data are not only Ghanaians but some visit our herbal centre from other west African countries in spite of the other centres having testing devices but our unique herbal treatment makes the difference.
Victoria Klepsch
Medical University Innsbruck, Austria
Title: Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T-cell signaling switch and emerging target in cancer immunotherapy
Time : 10:00-10:25
Biography:
Victoria Klepsch has received her PhD degree from the Medical University Innsbruck. She is a Postdoctoral Fellow at the Medical University Innsbruck in Gottfried Baier’s Lab. She has published 3 papers in well-reputed journals and has been working on NR2F6 and tumor immunology since 4 years continuing investigating in depth in this nuclear receptor NR2F6 in T-cell biology and cancer immunity.
Abstract:
Modulation of the immune system for the treatment of primary and metastatic tumors in cancer patients has been a goal for many decades. Very recently, blockade of immune checkpoints CTLA-4 and PD-1 has emerged as promising cancer immune therapies. Even though encouraging, there is an unmet medical need as still only a very limited number of patients respond to and are potentially cured by these therapies. In contrast to cell surface checkpoints, there are cancer therapeutic targets that are located inside the immune cells and are amenable to pharmacological modulation. Based on our published and unpublished findings that genetically NR2F6-deficient mice are able to immunologically reject otherwise lethal tumor burdens; we have identified and preclinically validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2, group F, member 6; alias Ear2 and COUP-TFIII) as a bona fide immune checkpoint. We could show that genetic ablation of NR2F6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, NR2F6-/- mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor re-challenge. This is paralleled by increased frequencies of both CD4+ and CD8+ T-cells and higher expression levels of interleukin-2 and interferon-ï§ at the tumor site. This defines NR2F6 as an intracellular and potentially also druggable immune checkpoint, where the presence of NR2F6 limits effector T-cell activation within the tumor microenvironment governing the amplitude of anti-cancer immunity, representing a promising avenue for development of alternative immune checkpoint inhibition treatment regimens.
Joanie Del Bano
Aix-Marseille University, France
Title: Bispecific antibodies in breast cancer immunotherapy
Time : 10:25-10:50
Biography:
Joanie Del Bano is a Pharmacist Resident and also pursuing PhD in Immuno-Oncology at the University of Aix-Marseille in the team "Therapeutic Antibodies and Immuno-targeting" led by Drs Daniel Baty and Patrick Chames. She is pursuing Pharmacy Residency Program at Marseille Public University Hospital. She is working on the development of bispecific antibodies for breast cancer immunotherapy.
Abstract:
Over the past 15 years, mounting evidence of the key contribution of NK cells in immunity against cancer has boosted the investigations into NK cell-based therapies. Among these strategies, antibody-based therapeutics is currently the fastest growing segment of the drug and biological market. However, tumor-targeting antibodies often have to face up an exhausted tumor environment responsible for their suboptimal effectiveness. Our objective is to manipulate NK cell functions and tumor targets using an original format of nanobody-based bispecific antibodies (bsFab) to revert the dampened immune response for treating breast cancer. Treatment and outcomes of HER2-amplified breast cancers have been revolutionized by the approval of trastuzumab. However, significant proportions of HER2 positive breast cancer are or become resistant due to de novo or acquired resistances. As well, triple negative breast cancers (TNBC) are intrinsically insensitive to most of the current targeted therapies such as hormonotherapy or trastuzumab. These cancers of poor prognosis remain a clinical challenge despite therapeutic innovations. We generate bispecific formats that display a unique, specific and high affinity for FcγRIII on NK cells and a moderate affinity for two tumor associated antigens: HER2 and mesothelin overexpressed in a large proportion of TNBC. NK antitumor effects driven by trastuzumab and bsFabs, alone or in combination, were investigated on different 2D and 3D breast cancer models. Our data underline the potential of these bsFabs to enlarge the number of patients eligible for breast cancer immunotherapy and prompt to consider combination strategies.
Shimae Nafarzadeh
Babol University of Medical Sciences, Iran
Title: Role of mast cells in oral squamous cell carcinoma
Time : 11:10-11:35
Biography:
Shimae Nafarzadeh has completed her DDS in Dentistry in 2004 and Specialty in Oral and Maxillofacial Pathology in 2007 from Shahid Beheshti University of Medical Sciences, Tehran, Iran. She has been working as a University Professor in the Oral and Maxillofacial Pathology Department of Babol Dentistry School since 2007 and recently became the Dean of the Department.
Abstract:
There are controversial findings about the role of mast cells in tumor progression. Some researchers believe mast cells play role in immunologic host defense, while some believe mast cells role in tumor progression. We conducted a systematic review article by surfing the PubMed and Scopus data bases and found 14 articles from 2000 to 2015. Mast cells are considered to have diverse biological functions such as phagocytosis, antigen processing, release of cytokines and preformed or newly formed mediators, hemostasis and inflammation. Mast cells also can affect angiogenesis by producing factors such as Heparin, Histamine, VEGF, Chymase, b-FGF, TGF-beta which certainly influence tumor growth. Role of mast cells as MMP activators has been identified. MMP-9 plays an important role in tumor metastasis and invasion through affecting angiogenesis and cleaving basement membrane. Considering poor prognosis of OSCC in spite of new therapeutic methods, it seems that mast cells could be good targets for future research and finding ways for their disactivation and suppression of their secretions is of great value for producing future anticancer drugs.