ABSTRACT
In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vß repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.
Subject(s)
Adoptive Transfer , Cerebellar Neoplasms , Immunotherapy, Adoptive , Medulloblastoma , Receptors, Antigen, T-Cell, alpha-beta/immunology , T-Lymphocytes , Animals , Cell Line, Tumor , Cerebellar Neoplasms/immunology , Cerebellar Neoplasms/therapy , Humans , Medulloblastoma/immunology , Medulloblastoma/pathology , Medulloblastoma/therapy , Mice , Mice, Transgenic , T-Lymphocytes/immunology , T-Lymphocytes/pathologyABSTRACT
The paper includes the data concerning the taxonomic status of the agent of cereals pale-green dwarf (ACPGD) which has been defined as the phytopathogenic variant of the mollicute Acholeplasma laidlawii and called A. laidlawii var. granulum. Since besides phytopathogenicity ACPGD has such fundamental differences from A.laidlawii as: a very large genome of 2200 thousand pairs of nucleotides (t.p.n.) to 2310 t.p.n. that practically equals a sum of genomes of A. laidlawii (1600 t.p.n.) and phytoplasmas (710 t.p.n.); two forms of DNA-dependent RNA-polymerase (one form functions in A. laidlawii); a capacity to form extracellular fructosobisphos-phatase which looks like its hypothetical phylogenetic precursor a bacteria Bacillus subtilis; availability of numerous fermentative activities which are absent in acholeplasmas; peculiar relation to sterols availability in nutrient media that is not characteristic of all the known acholeplasmas; extremely rich, as to quantity and quality, composition of antigens to react almost homologously with antibodies to representatives of Acholeplasma genus and separate species of Mycoplasma genus; great similarity (above 88 %) of sequences of 16S rRNA of ACPGD and representatives of Phytoplasma genus and other properties described in the paper, so it is concluded, that proceeding from its characteristics, ACPGD cannot be referred to either of the existing genera of the Mollicules class, because according to all its features this mollicute is a transition form of the microorganism, it is the hitherto unknown chain between these genera of mollicutes and sporiferous bacteria, ACPGD is a probable representative of mollicute precursor with genome of about 1600 t.p.n. and, first of all, of genera Acholeplasma and Phytoplasma which arised as a result of the evolutionary splitting of its genome. On this basis, it is recommended to found for ACPGD in the Mollicutes class, order III Acholeplasmatales, family I Acholeplasmataceae, a new genus II Pluraplasma gen. nov. and its first species Pluraplasma granulum sp. nov., the strain 118 being its typical representative.