Good news! Cancer is history soon! Very recommendable article!
"... A new study at the Weizmann Institute of Science, published in Cell, paves the way toward an immunotherapy that will exploit a different, previously unused immune system weapon: naturally produced antibodies. ...
In the past few years, naturally occurring antibodies have commonly been found in cancerous tumors, but their purpose was unknown ...
In attacking this enzyme, some of the antibodies had undergone an evolution of sorts: They had accumulated mutations that improved their fit to the tumor, and specifically, to this enzyme. “We didn’t expect to see such evolution around cancer,” ...
one potential reason may be the immune system’s exhaustion. Whereas fighting an infection may take a week, cancer develops over months, or even years, finding ways to avoid the patient’s immunity. “After trying to fight the cancer over such a long time, the immune system may be too exhausted to supply a full set of weapons needed for effectively killing the tumor – for example, the natural killer cells that are needed for this purpose in addition to the antibodies,” ...
Indeed, the researchers found that very few natural killer cells were present in the tissue samples obtained from patients with ovarian tumors. But when they added such cells and antitumor antibodies together to tissue cultures, the killer cells excelled at destroying the tumors. ..."
Next followed nearly six years of research, in the course of which ... scientists ... proved that natural antibodies in cancerous tissue mount a targeted attack on the tumor, binding to its molecules in a precise fit. The researchers then sequenced genomes of intratumor B cells and identified different gene segments encoding antibodies that bind to the tumor.
Perhaps most important, they managed to identify – out of the thousands of proteins in cancer cells – a molecule that is targeted by the newly identified antibodies: an enzyme called MMP14 (MT1-MMP), a membrane-bound protease. In the healthy body, this scissor-like enzyme plays important roles in remodeling tissues – for example, during regeneration or wound healing. In cancer it operates in the tumor’s microenvironment and gets out of control, cutting through the matrix around the cancer cells and thus helping them invade the surrounding tissue and spread to other organs, causing metastasis. The researchers found that the ovarian tumors in their study contained abnormally high levels of the MMP14 enzyme. ...In attacking this enzyme, some of the antibodies had undergone an evolution of sorts: They had accumulated mutations that improved their fit to the tumor, and specifically, to this enzyme. “We didn’t expect to see such evolution around cancer,” ...
one potential reason may be the immune system’s exhaustion. Whereas fighting an infection may take a week, cancer develops over months, or even years, finding ways to avoid the patient’s immunity. “After trying to fight the cancer over such a long time, the immune system may be too exhausted to supply a full set of weapons needed for effectively killing the tumor – for example, the natural killer cells that are needed for this purpose in addition to the antibodies,” ...
Indeed, the researchers found that very few natural killer cells were present in the tissue samples obtained from patients with ovarian tumors. But when they added such cells and antitumor antibodies together to tissue cultures, the killer cells excelled at destroying the tumors. ..."
The abstract sounds rather complicated.
From the abstract:
"The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC). Patient-derived tumor cells were frequently coated with IgGs. Intratumoral ASCs in HGSOC were both mutated and clonally expanded and produced tumor-reactive antibodies that targeted MMP14, which is abundantly expressed on the tumor cell surface. The reversion of monoclonal antibodies to their germline configuration revealed two types of classes: one dependent on SHMs for tumor binding and a second with germline-encoded autoreactivity. Thus, tumor-reactive autoantibodies are either naturally occurring or evolve through an antigen-driven selection process. These findings highlight the origin and potential applicability of autoantibodies directed at surface antigens for tumor targeting in cancer patients."
Natural anticancer antibodies (green) bound to a single ovarian tumor cell; the cell’s nucleus is in blue. Viewed with confocal microscopy
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