Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.

Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.

Police is Dead: On the Birth of Economism

Police is Dead is an historiographic analysis whose objective is to change the terms by which contemporary humanist scholarship assesses the phenomenon currently termed neoliberalism. It proceeds by building an archeology of legal thought in the United States that spans the nineteenth and twentieth centuries. My approach assumes that the decline of certain paradigms of political consciousness set historical conditions that enable the emergence of what is to follow. The particular historical form of political consciousness I seek to reintroduce to the present is what I call “police:” a counter-liberal way of understanding social relations that I claim has particular visibility within a legal archive, but that has been largely ignored by humanist theory on account of two tendencies: first, an over-valuation of liberalism as Western history’s master signifier; and second, inconsistent and selective attention to law as a cultural artifact. The first part of my dissertation reconstructs an anatomy of police through close studies of court opinions, legal treatises, and legal scholarship. I focus in particular on juridical descriptions of intimate relationality—which police configured as a public phenomenon—and slave society apologetics, which projected the notion of community as an affective and embodied structure. The second part of this dissertation demonstrates that the dissolution of police was critical to emergence of a paradigm I call economism: an originally progressive economic framework for understanding social relations that I argue developed at the nexus of law and economics at the turn of the twentieth century. Economism is a way of understanding sociality that collapses ontological distinctions between formally distinct political subjects—i.e., the state, the individual, the collective—by reducing them to the perspective of economic force. Insofar as it was taken up and reoriented by neoliberal theory, this paradigm has become a hegemonic form of political consciousness. This project concludes by encouraging a disarticulation of economism—insofar as it is a form of knowledge—from neoliberalism as its contemporary doctrinal manifestation. I suggest that this is one way progressive scholarship can think about moving forward in the development of economic knowledge, rather than desiring to move backwards to a time before the rise of neoliberalism. Disciplinarily, I aim to show that understanding the legal historiography informing our present moment is crucial to this task.