NEWS
PHARMACEUTICALS
CAR-T before cancer course ANTHONY KING
CAR-T therapy involves taking a patient’s own immune T cells out of their body, tweaking them genetically to target cancer cells and returning them to the patient. The first market approvals of CAR-T therapies were granted by the US Food and Drug Administration (FDA) in 2017 to Kite Pharma, recently bought by Gilead, and Novartis. Now, UK company Autolus has found
a way to exploit CAR-T to target a sort of cancer for which few treatment options exist: cancer of the body’s T cells, also called T cell lymphoma and the most common form of blood cancer. There are two types of T cell populations, with either a TRBC1 or a TRBC2 receptor. ‘Malignancies form from a single cell and so the cancer is going to have either TRBC1 or TRBC2,’ explains Martin Pule at University College London and founder of Autolus.
ENERGY Better water-splitting catalyst ANTHONY KING
A new catalyst has been developed for artificial photosynthesis, allowing water to be split more efficiently into protons and oxygen gas. The catalyst is made by combining nickel, iron, cobalt and phosphorus – inexpensive elements that pose few safety hazards. It was synthesised at room temperature with inexpensive equipment (Nature Chem.; doi:10.1038/nchem.2886). Artificial photosynthesis seeks
to perform two reactions that plants achieve using a complex series of enzymes. It does so via an electrochemical process, akin to a battery. ‘The anode side is where you split water to get oxygen
gas and protons and electrons,’ says Phil De Luna at the University of Toronto, Canada. ‘On the cathode side, the same protons and electrons are combined with carbon dioxide to electrochemically reduce it to form products like hydrocarbons.’ For this paper, the lab generated carbon monoxide, but ethanol or methanol are also viable end products. Water is an extremely
stable molecule, so requires an excellent catalyst that lowers the energy barrier for the splitting reaction. Previously, the oxygen evolution side favoured a catalyst that works at a more alkaline pH, whereas the carbon dioxide reduction traditionally ran better at neutral pH. The new system is more energy efficient as the new
anode catalyst also performs best at neutral pH. When combined with a
superior CO2 reduction catalyst,
which the team reported in 2016, the system achieved an electrical-to-chemical power conversion efficiency of 64%, the highest value achieved for such a system. ‘The breakthrough here is
to expand on the relatively small number of known electro- catalysts that can operate in water at neutral pH. This is
important as with most CO2 reduction electrodes the highest current densities and best selectivities for carbon products are achieved at neutral pH,’ says Alexander Cowen, catalytic systems chemist at the University of Liverpool, UK. ‘One of the
great things about this catalyst is that it is made from relatively low-cost elements, which should make it possible to scale-up.’ The combined system of anode and cathode would be placed in what would look like a large electrochemical cell system and hooked into a CO2
emitting facility such as a
coal fired power plant. Carbon monoxide generated can be used to make synthetic fuels and other chemicals. However, some challenges
remain, particularly on the CO2 reduction side, says Cowen. ‘For
example, in this study a gold electrode is used, leading to potential cost and poisoning
issues, especially if industrial CO2 streams such as flue gas are to be employed.’
As a proof of concept, healthy T cells
were taken from a mouse and edited to have surface proteins that targeted TRBC1. These recognised and killed all T cells with the TRBC1 receptor in a mouse with leukemia, healthy and cancerous. However, the other half of the mouse T cells – those with TRBC2 – survived (Nature Medicine; doi:10.1038/ nm.4444). ‘By preserving half the T cells, we think the patient will do just fine. Immunosuppression will not be noticeable and the rest of the immune system will fill in the gaps,’ says Pule. The survival of these T cells is key.
CAR-T has been successfully used in B cell cancers by targeting all B cells – healthy and cancerous – but the patient can tolerate B cell wipe out. However, the loss of all T cells in a patient would lead to unacceptable suppression of their immune system. ‘The problem with cancer is that it
generally comes from normal cells in our body that have gone wrong and our immune system is not particularly interested in these cells,’ Martin Pule explains. ‘In CAR-T therapy, you can imagine the T cells as like hardware that is reprogrammed so they look for cancer cells instead.’
Clinical trials planned for 2018 at
University College London Hospital will treat patients with the two commonest subtypes of T cell cancer. ‘This is a very clever approach to target a subset of T cells. A similar approach has been proposed in myeloma and B cell malignancies where antibodies are divided in a 60% to 40% ratio of IgKappa light chain and IgLamda light chain,’ notes immunotherapist Carl June at the University of Pennsylvania. ‘The most serious risk with this approach is the induction of autoimmunity due to reduction in the repertoire of T regulatory cells.’
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JAMES CAVALLINI/SCIENCE PHOTO LIBRARY
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