Novel immune-oncology approach for potential cancer treatment

A research collaboration between Monash University and Lava Therapeutics details a novel immune-oncology approach for the potential treatment of cancer. Instrumental to the study was co-first author Dr Roeland Lameris from Amsterdam UMC and colleagues from the University of Melbourne.

Published in Nature Cancer, the study, co-led by Monash Biomedicine Discovery Institute’s ARC Laureate Fellow Professor Jamie Rossjohn and Dr Adam Shahine,  highlights the synergy between an antibody fragment, known as a nanobody, that not only acts as a bridge helping to link together two key immune cell receptors but also takes advantage of their interaction, enabling the body to enhance its immune response to cancer.

These antibody fragments, denoted as nanobodies, act by targeting the interaction between a molecule known as CD1d and Natural Killer T cells (NKT) in a stable and long-lasting manner, against tumour samples of patients with multiple myeloma and acute myeloid leukemia.

The new findings will serve as a model for the potential generation of new and effective therapies against a broad range of cancers.

Using the Australian Synchrotron, the team at Monash University provided detailed atomic insight into how the nanobodies exerted their effect on immune cells in a cancer model. “We were able to precisely visualize how the nanobody simultaneously recognized CD1d and the NKT TCR, thereby providing a molecular basis for their anti-tumour properties” Professor Rossjohn stated.

Hans van der Vliet, professor in medical oncology at Amsterdam UMC and chief scientific officer of Lava Therapeutics says “By targeting and boosting natural immune cells that are inherent in all humans, such as NKT cells and gamma-delta T cells, for an enhanced therapeutic effect, we believe our approach could ultimately translate into a broadly applicable immunotherapeutic approach for a range of cancer indications.”

“This collaborative work paves the way for rationally developing improved therapeutics to treat a range of cancers” said co-first author Dr. Shahine.

Read the full paper in Nature Cancer titled: “A single domain bispecific antibody targeting CD1d and the NKT T cell receptor induces a potent anti-tumour response
DOI: 10.1038/s43018-020-00111-6

Original paper

Image: Nanobodies targeting of a tumour cell.

Image Credit: Erica Tandori

Immutep and Monash University Receive Grant Funding for LAG-3 Project

SYDNEY, AUSTRALIA – Immutep Limited (ASX: IMM; NASDAQ: IMMP) is pleased to announce that the Australian Research Council (ARC) has awarded Immutep and research partner Monash University a A$360,000 grant under the ARC‘s Linkage Project scheme to support their research collaboration into Lymphocyte Activation Gene-3 (LAG-3) for a further three years.

The collaboration between Immutep and Monash University’s Biomedicine Discovery Institute (BDI) commenced in 2017 and the parties have been investigating the structure of LAG-3 and how it binds to its main ligand, MHC Class II. This new funding will allow further investigation and provide insights into the way LAG-3 controls T cell function, and may ultimately lead to the development of a new generation of innovative medicines for the treatment of cancer, autoimmune diseases or infectious diseases.

ARC Laureate Fellow at the Monash BDI, Professor Jamie Rossjohn, said: “We thank the ARC for the continued funding to support our collaboration with Immutep. Through the partnership, we are able to combine the state-of-the-art structural biology facilities we have here at the BDI with the expertise of Dr Triebel, who is the pioneer of the LAG-3 immune checkpoint. This is important work and we look foward to furthering our understanding of LAG-3 structure and function.”

Immutep‘s CSO and CMO, Dr Frederic Triebel, also welcomed the grant and said: “We have been very pleased to collaborate on this project alongside one of the leading international groups in structural immunology led by Professor Rossjohn. We look foward to continuing our studies into LAG-3 and are most grateful, of course, for the support of the ARC.”

The title of the new grant is “Investigating the atomic structure of an immune cell inhibitory receptor” andwill be conducted over a three year period. Professor Rossjohn will have overall oversight of the project and will be responsible for resources management of the grant. As the leading global authority on LAG-3, Dr Triebel will provide his expertise and facilitate access to relevant LAG-3 specific constructs, reagents and antibodies directed against LAG-3. Immutep will also make a financial contribution towards the study.


About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. The research teams are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

Professor Jamie Rossjohn FAA FLSW FMedSci Professor Jamie Rossjohn is an Australian Research Council Laureate Fellow at Monash Biomedicine Discovery Institute, Monash University and Professor in Structural Immunology at Cardiff University.  Professor Rossjohn is recognized for his contributions to understanding molecular bases of immunity.

About Immutep

Immutep is a globally active biotechnology company that is a leader in the development of LAG-3 related immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value to shareholders. Immutep is listed on the Australian Securities Exchange (IMM) and on the NASDAQ (IMMP) in the United States.

Immutep’s current lead product candidate is eftilagimod alpha (“efti” or “IMP321”), a soluble LAG-3 protein (LAG-3Ig) based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a chemoimmunotherapy for metastatic breast cancer termed AIPAC (clinicaltrials.gov identifier NCT02614833); a Phase II clinical trial being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as “MSD” outside the United States and Canada) referred to as TACTI-002 to evaluate a combination of efti with KEYTRUDA® (pembrolizumab) in several different solid tumours (clinicaltrials.gov identifier NCT03625323); a Phase I clinical trial being conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. referred to as INSIGHT-004 to evaluate a combination of efti with avelumab (clinicaltrials.gov identifier NCT03252938); and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel (clinicaltrials.gov identifier NCT02676869).

Additional LAG-3 products, including antibodies, for immune response modulation in autoimmunity and cancer are being developed by Immutep’s large pharmaceutical partners. Immutep is also developing an agonist of LAG-3 (IMP761) for autoimmune disease.

Further information can be found on the Company’s website www.immutep.com or by contacting:

Australian Investors/Media:
Catherine Strong, Citadel-MAGNUS
+61 (0)406 759 268; cstrong@citadelmagnus.com

U.S. Media:
Tim McCarthy, LifeSci Advisors
+1 (212) 915.2564; tim@lifesciadvisors.com

This announcement was authorised for release by the Board of Immutep Limited.

Original article

postdoc

Congratulations to Adam

Winner of the Early Career Researcher Publication Prize for 2020

Robert Porter Early Career Researcher Publication Prize for Laboratory Based Sciences

Dr Adam Shahine, Department of Biochemistry & Molecular Biology, Biomedicine Discovery Institute, School of Biomedical Sciences

The Faculty of Medicine, Nursing and Health Sciences (MNHS) is committed to developing Faculty-based Early Career Researcher (ECR)* initiatives, to assist our ECRs in the development of their research careers. In addition to the emphasis placed on a strong track record in research publications and competitive funding, there is also the requirement for ECRs to secure competitive Prizes & Awards. In support of this, the Faculty Research Office offers the MNHS ECR Publication Prize.

*In FMNHS, an Early Career Researcher (ECR) is defined as academic staff (Levels A-C) within 10 years of their PhD conferral (taking career disruptions into account).

ECRs are invited to nominate one research publication from the previous year for the MNHS ECR Publication Prize.

A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids Nature Communications

Adam says: It is an absolute honour to be the recipient of the Robert Porter for Laboratory Based Sciences for this publication. I would like to acknowledge all co-authors and collaborators who took part in this exciting study. In particular, I’d like to thank my key supervisor and mentor Professor Jamie Rossjohn. This study married together flow cytometry, mass spectrometry, surface plasmon resonance, and x-ray crystallography, to describe the breadth of membrane phospholipids presented by the antigen presenting molecule CD1b, and the mechanisms of presentation to autoreactive T cells first isolated and characterised here. The importance of phospholipid antigen presentation has only been recently realised, which in the context of CD1b, have been found to mediate autoimmune diseases including T cell lymphoma and skin inflammation. One of the key findings from this study include the crystal structure of CD1b presenting a membrane phospholipid to a T cell receptor, which for the first time, may pave the way to understanding how these diseases occur. From this study, I was privileged to present this research at the CD1-MR1 EMBO Workshop conference in Oxford, UK in 2019, as well as Lorne Infection & Immunity and Lorne Proteins conferences in 2020.