Profile: Dr Micheal A. Morse

Dr Morse is a regular and invaluable contributor to Expert Opinion on Biological Therapy, having joined the Editorial Board in 2000 and accepting the position of Editor-in-Chief in 2007. He is currently Associate Professor of Medicine at Duke University, and is a G.I. Oncologist at Duke Comprehensive Cancer Center, where his clinical expertise lies in the treatment of gastrointestinal and hepatic malignancies, and malignant melanoma.

Dr Morse’s research focuses on developing strategies to activate T cell responses against tumors by immunizing patients with dendritic cell based vaccines. His group has continued to develop modifications to these vaccines, including loading with antigen in the form of peptides, mRNA, viral vectors and maturing dendritic cells with cytokines. Most recently, they have focused on genetically altering the expression of co-stimulatory and adhesion molecules, and have also identified preliminary data which suggests that it may be important to activate antibody responses as well as T cells in order to initiate immune-mediated destruction of tumors. The group is also working on other methods of modulating immune response, including anti-CTLA4 antibodies and strategies that interfere with inhibitory molecules such as PDL1. Further areas of research include other anti-cancer therapies to weaken the tumor’s ability to impair immune response, including combinations of cancer vaccines along with chemotherapy, radiotherapy, and targeted therapies.

Dr Morse has contributed many papers to Expert Opinion on Biological Therapy during his time on the Editorial Board, including his recent papers listed below:

Countering tumor-induced immunosupression during immunotherapy for pancreatic cancer
Michael A Morse Joseph Robert Hall, Janet MD Plate
Expert Opinion on Biological Therapy, Mar 2009, Vol. 9, No. 3, Pages 331-339.

Update on anti-CTLA-4 antibodies in clinical trials
Lee F Langer, Timothy M Clay, Michael A Morse
Expert Opinion on Biological Therapy, Aug 2007, Vol. 7, No. 8, Pages 1245-1256.

Vascular endothelial growth factor and immunosupression in cancer: current knowledge and potential for new therapy
Benjamin F Johnson, Timothy M Clay, Amy C Hobeika, H Kim Lyerly, Michael A Morse
Expert Opinion on Biological Therapy, Apr 2007, Vol. 7, No. 4, Pages 449-460.

In vitro evaluation of immunotoxicity

Recommended in 2000 by EMEA's Committee of Proprietary Medicinal Products,the in vitro assessment of immunotoxic risk for drug candidates is an integral part of preclinical safety screenings. Indeed, immunosuppression, immunostimulation, hypersensitivity and autoimmunity are adverse effects that can be elicited by (bio)pharmaceuticals.
A number of assays, available from CROs and reagent companies, can be used to test the effects of drugs, whether intended or not, on the various players of cell-mediated immunity. In a technical article to be published in the April issue of Expert Opinion on Drug Discovery, Dr Maria Fuggetta critically reviews a selection of these assays and suggests how enhanced methodologies can improve the identification of immunological hazard.

‘JUPITER’ and the risk of heart disease

Statins are blockbuster drugs taken by millions around the world. Results from the ‘JUPITER’ clinical trial[1] indicate that these cholesterol-lowering agents could decrease the risk of heart disease even for persons with low cholesterol levels; meaning that millions more could benefit from popping a statin pill…

But could they really? What indicators and risk factors dictate the prescription of statins? How should vascular risk be measured? And what are the factors that count towards this risk? An Editorial in the January 2009 issue of CMRO discusses the JUPITER study and explores these interesting themes.

The trial suggests that hsCRP, a protein associated with inflammation, can be used to identify subjects without vascular disease who should receive statins despite a low or intermediate calculated risk. The CMRO editorial highlights the fact that risk assessment needs to be re-examined, and discusses the role of hsCRP-testing in what the authors call risk stratification. The authors also feel that guidelines (and clinical practice) may need changing if indeed statins do have a much wider role in preventing vascular disease than was previously thought.

Of course, if relatively healthy persons (‘low or intermediate risk’) are to be prescribed statins, then there are terrific cost implications too. The authors of the editorial remark that this is all the more so if the benefits observed from taking Crestor (used in the JUPITER trial) can not be reproduced by cheaper, generic statins.

At the heart of the ongoing scientific debate, the fundamental question remains: do statins have a convincing role in primary prevention of heart disease? Read the editorial (an open access article) here find out what the authors think.

[1] JUPITER: Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

Impact of predictive pharmacokinetics

The implementation of studies aiming at predicting ADME properties at preclinical drug discovery stages has been central in the effort to reduce attrition rates.
In a clear and authoritative article reviewing the development, over the past three decades, of Discovery Metabolism and Pharmacokinetics research, Dr Summerfield analyses the key elements which moved the field forward and anticipates how new paradigms, such as translational medicine and systems thinking, will push it further.
He concludes that, although the predictive metabolism and pharmacokinetics approach already proved successful, a strong impact on drug pipelines will only be achieved when pharmacodynamics and toxicology are integrated in a similar way to drug discovery programmes.
The article will be available in the March issue of Expert Opinion on Drug Discovery

Challenges facing liposome-based targeted delivery of antithrombotic drugs

Haemorrhage is a major risk factor associated with administration of thrombolytic protein drugs. In vivo stability with conventional parenteral administration also remains a concern due to the intrinsic nature of thrombolytic protein drugs. Liposome-based delivery systems have been applied to other drugs in order to reduce toxicity, increase site specific action and protect against protein denaturation, but does the same apply to thrombolytic protein drugs and to what extent? Can liposome-based thrombolytic preparations reap the full benefits of this delivery system?

In the review article entitled “Liposomes for targeted delivery of antithrombotic drugs” Elbayoumi & Torchilin review the major work to date on liposome-based delivery of antithrombotic drugs to vascular pathology sites and provide their own perspective on the future of the field.

Will genomic technologies change the landscape of toxicology research?

With so many drug failures due to toxicity concerns, the development of more effective approaches to toxicity testing is of utmost importance. In their recent review “Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity,” Rusyn and Hege Harrill put forward the view that systems toxicology ‘offers the promise of more accurate predictions of adverse health effects in humans.’ They conclude that ‘Translational research bridging rodent and human toxicity will be the key to the success of this field.’ What will the impact of such approaches be on current gold standard? How widely used will they become?

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CXCR4 antogonists

Several CCR5 antagonists, which inhibit the entry of HIV-1 in the host cell, have proven a valuable strategy for the treatment of AIDS. However, the virus can switch to the CXCR4 co-receptor to enter cells, thus prompting the need for CXCR4 antagonists.
In a review published in the January issue of Expert Opinion on Therapeutic Patents, Dr Liotta explores the preclinical development of such compounds, and finds that this relatively recent field could offer therapeutic options in several disease areas.