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Tumor Discovery EpCAM-targeting cancer immunotherapies

dose indicated a satisfactory safety profile. VB4-845 was challenge the notion that existing neutralizing antibodies
shown to not be systemically absorbed but remained in the are a primary cause of immunogenicity to bacteria-
bladder until elimination, probably due to the molecular based rITs in humans. Furthermore, a clinical study of
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size of the drug and cellular integrity of the bladder. In MOC31PE was conducted with the aim of establishing
addition, VB4-845 was found to be specific to antigen- the efficacy of the rIT in the context of intraperitoneal
positive tumors. Although it induced an immunogenic administration in late-stage colorectal cancer patients
response, this expected outcome was attributed to the with confirmed peritoneal metastasis. The study was
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origin of the antibody fragment and the bacterial toxin. The conducted to analyze the local and systemic cytokine
authors proposed that tumor response may be saturated at response in these patient populations undergoing
higher doses due to the dose range of administered VB4- cytoreductive surgery and hyperthermic intraperitoneal
845 exceeding the drug concentration required to kill chemotherapy with or without intraperitoneal treatment
more than 99% of cells in EpCAM-positive bladder tumor with MOC31PE. The rIT activated local and systemic
cell lines. Thus, VB4-845 can safely inhibit the growth of cytokines, an added advantage that can potentiate its
tumors in high-grade EpCAM-positive NMIBC patients in antitumor activities. The investigators enrolled 21 and
a dose-dependent manner. 26 adult patients who were administered with or without

Another rIT evaluated against EpCAM-positive MOC31PE, respectively. A tumor debulking cytoreductive
cancers is MOC31PE consisting of the full murine MOC31 surgery baseline treatment was performed on all patients
IgG1 monoclonal anti-EpCAM antibody covalently before receiving the rIT as a single rapid intraperitoneal
linked to the complete Pseudomonas exotoxin A (PE) instillation through two abdominal drainage catheters. To
was investigated in metastatic colorectal cancer patients assess cytokine responses, the authors analyzed 27 growth
in a phase I clinical study. Because the main limitation factors, chemokines, IFN, and pro- and anti-inflammatory
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of rITs is immunogenicity, MOC31PE was administered interleukins in serum and intraperitoneal fluids. Higher
intravenously with and without the immunosuppressant levels of pro-inflammatory cytokines were observed in the
cyclosporine. The aim was to minimize the generation MOC31PE group compared to patients who did not receive
of systemic antidrug immunogenic responses. The the rIT, with time-dependent variability. In addition,
administration of MOC31 as monotherapy demonstrated elevated levels of innate proinflammatory cytokines, TNF,
improved overall survival (12.7 versus 6.2 months) and a time-response curve for the strong T-cell stimulator
in a cohort of colorectal cancer patients compared to IFN and its associated chemokine IFNγ-induced protein/
combination therapy with immunosuppressant. Second, chemokine (C-X-C motif) ligand 10 (IP-10) were noted in
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another study investigated the safety and maximum the serum of patient who received the rITs. Inferentially,
tolerable doses in patients diagnosed with EpCAM-positive elevated pro-inflammatory cytokines are associated with
tumors in combination with immunosuppression. The the induction of immunogenic cell death and have the
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study included 63 patients divided into three groups: 34 potential to overturn “cold” tumors into immunologically
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received MOC31PE alone, 23 received MOC31PE in “hot.” The study concluded that the overall survival in
conjunction with IV cyclosporine, and the remaining six approximately 78% of patients was 3 years, with 53%
were administered MOC31PE and cyclosporine orally. achieving an overall survival rate of up to 5 years. In
Inclusion criteria include adults 18 years or older, ECOG contrast, an intensified local inflammatory response was
performance status of 0 – 2, and evidence of at least 10% not found to adversely affect long-term outcomes. The
EpCAM-positive metastatic carcinoma. In addition, authors reported a compartmentalized inflammatory
conventional treatments were discontinued 4 weeks before response in the peritoneal cavity that correlates with the
and during the study. MOC31PE was administered up localized response, which was further enhanced by the
to 4 times every 2 weeks, while cyclosporine was given peritoneal infusion of MOC31PE.
1 day before MOC31PE and continued for four days post- 7. Bi-specific T-cell engagers (BiTEs)
initial administration. At the end of the study, the authors
observed that patients undergoing monotherapy had BiTEs are a relatively new class of monoclonal antibodies
better therapeutic outcomes compared to those receiving that drive T-cells to cancer cells by binding to T-cells specific
combination therapy. Conceivably, the efficacy of the antigen (usually CD3) and tumor-specific surface antigens
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rIT was compromised by the coadministration of the simultaneously. For EpCAM-specific BiTEs, one arm of
immunosuppressant in the combination therapy group, the antibody binds to T-cells, whereas the others recognize
as in previous studies. 25,26 indicated that MOC31PE can and bind to EpCAM. Catumaxomab is a chimeric (rat-
induce an unexplained antitumor immune response that murine) bispecific and trifunctional antibody that combines
can provide additional antitumor activities. These findings the qualities of bispecific molecules and traditional

Volume 4 Issue 1 (2025) 5 doi: 10.36922/td.4926