Immunohistochemical detection of EGFRvIII in glioblastoma - Anti-EGFRvIII antibody validation for diagnostic and CAR-T purposes.

The emergence of therapies such as CAR-T has created a need for reliable, validated methods for detecting EGFRvIII in patient tumor cells. Particularly so since previous studies have already suggested that some anti-EGFRvIII antibodies may be non-specific. The present paper evaluates the use of the L8A4 antibody in the immunohistochemical (IHC) and immunocytochemical (ICC) detection of EGFRvIII in 30 glioblastoma specimens, and compares it with other methods such as RT-PCR, MLPA, and FISH. The results indicate that Real-time PCR appears to be a very specific and sensitive method of EGFRvIII detection. ICC analysis with L8A4 also appears specific but requires cell culture. IHC analyses of EGFRvIII returned a number of false positives when using L8A4. Due to the growing need for an effective diagnostic tool before starting immunotherapy methods, such as the CAR-T anti-EGFRvIII or SynNotch CAR-T recognizing EGFRvIII, it is necessary to identify a more reliable and simple method of EGFRvIII detection or improve the specificity of the anti-EGFRvIII antibody, until then, immunocytochemistry may temporarily replace immunohistochemistry.

Optimizing sequestered carbon in forest offset programs: balancing accounting stringency and participation.

BACKGROUND: Although there is broad agreement that negative carbon emissions may be required in order to meet the global climate change targets specified in the Paris Agreement and that carbon sequestration in the terrestrial biosphere can be an important contributor, there are important accounting issues that often discourage forest carbon sequestration projects. The legislation establishing the California forest offset program, for example, requires that offsets be "real, additional, quantifiable, permanent, verifiable, and enforceable". While these are all clearly desirable attributes, their implementation has been a great challenge in balancing complexity, expense, and risk. Most forest offset protocols carry similar accounting objectives, but often with different details, (e.g. Richards and Huebner in Carbon Manag 3(4):393-410, 2012 and Galik et al. in Mitig Adapt Strateg Glob Change 14:677-690, 2009). The result is that the complexity, expense, and risk of participation discourage participation and make it more difficult to achieve climate mitigation goals. We focus on the requirements for accounting and permanence to illustrate that current requirements disproportionately disadvantage small landowners. RESULTS: The simplified 1040EZ filing system for U.S. income taxes may provide insight for a protocol model that balances reward, effort, and risk, while still achieving the overall objectives of standardized offset protocols. In this paper, we present initial ideas and lay the groundwork behind a "2050EZ" protocol for forest carbon sequestration as a complement to existing protocols. CONCLUSION: The Paris Agreement states that "Parties should take action to conserve and enhance, as appropriate, sinks and reservoirs of greenhouse gases." The Paris Agreement also refers to issues such as equity, sustainable development, and other non-carbon benefits. The challenge is to provide incentives for maintaining and increasing the amount of carbon sequestered in the biosphere. Monitoring and verification of carbon storage need to be sufficient to demonstrate sequestration from the atmosphere while providing clear incentives and simple accounting approaches that encourage participation by diverse participants, including small land holders.