A Review of Monoclonal Antibody-Based Treatments in Non-small Cell Lung Cancer

Panahi, Yunes; Mohammadzadeh, Amir; Behnam, Behzad; Orafai, Hossein; Jamialahmadi, Tannaz; Sahebkar, Amirhossein

doi:10.1007/978-3-030-55035-6_3

Cited by 9 publications

(4 citation statements)

References 110 publications

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“…A subset of NSCLC patients present with tumors whose biology is driven by expression of mutated active forms of ERBB1. Some of the mutant ERBB1 proteins are point mutation mutants and others are deletion mutants ( 10 , 11 ). Multiple ERBB1 inhibitors are approved to treat this form of the disease including erlotinib, afatinib, and recently osimertinib.…”

Section: Introductionmentioning

confidence: 99%

“…The treatment of NSCLC over the past 20 years has been revolutionized, first by the development of the pemetrexed carboplatin drug combination and then subsequently by checkpoint inhibitory immunotherapy (10)(11)(12)(13)(14). For NSCLC tumors expressing mutant RAS proteins or without a clear oncogenic driver, the combination of pemetrexed, carboplatin, and an anti-PD1 antibody, e.g., pembrolizumab, is a standard of care therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

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GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins

et al. 2021

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We determined the molecular mechanisms by which the novel therapeutic GZ17-6.02 killed non-small cell lung cancer (NSCLC) cells. Erlotinib, afatinib, and osimertinib interacted with GZ17-6.02 to kill NSCLC cells expressing mutant EGFR proteins. GZ17-6.02 did not interact with any EGFR inhibitor to kill osimertinib-resistant cells. GZ17-6.02 interacted with the thymidylate synthase inhibitor pemetrexed to kill NSCLC cells expressing mutant ERBB1 proteins or mutant RAS proteins or cells that were resistant to EGFR inhibitors. The drugs interacted to activate ATM, the AMPK, and ULK1 and inactivate mTORC1, mTORC2, ERK1/2, AKT, eIF2α; and c-SRC. Knockdown of ATM or AMPKα1 prevented ULK1 activation. The drugs interacted to cause autophagosome formation followed by flux, which was significantly reduced by knockdown of ATM, AMPKα1, and eIF2α, or by expression of an activated mTOR protein. Knockdown of Beclin1, ATG5, or [BAX + BAK] partially though significantly reduced drug combination lethality as did expression of activated mTOR/AKT/MEK1 or over-expression of BCL-XL. Expression of dominant negative caspase 9 weakly reduced killing. The drug combination reduced the expression of HDAC2 and HDAC3, which correlated with lower PD-L1, IDO1, and ODC levels and increased MHCA expression. Collectively, our data support consideration of combining GZ17-6.02 and pemetrexed in osimertinib-resistant NSCLC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins

et al. 2021

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“…Antibodies are proven to be an increasingly important class of therapeutics due to their invaluable advantages such as high specificity and high affinity [7]. They are already widely in use for the treatment of lung diseases such as lung cancer [8] and severe asthma [9]. In response to the COVID-19 pandemic, together with the advances in antibody engineering, the landscape of antibody therapeutics has rapidly revolutionized.…”

Section: The Need For a New Strategy To Combat Respiratory Viral Infe...mentioning

confidence: 99%

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

Chow

Pan²,

Seow³

et al. 2023

Trends in Pharmacological Sciences

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“…Targeted monoclonal antibodies are currently being applied in clinical trials because these antigens play an important role in tumor proliferation, survival, angiogenesis, and metastasis( 12 13 ). Despite the advantages of specificity, monoclonal antibodies are unsuccessful in therapeutic applications caused by tumor heterogeneity and redundancy of molecular pathways leading to cancer cell survival, and there are still concerns with high recurrence rates and medication resistance( 14 ). Bispecific antibodies are molecules that have been engineered to bind to two distinct antigens simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Enhanced in vivo anti-tumor efficacy of whole tumor lysate in combination with whole tumor cell-specific polyclonal antibody

Khanahmad

Rahimmanesh²,

Esmaili³

et al. 2023

Res Pharma Sci

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Background and purpose: Despite the widespread utilization of cancer vaccines with specified antigens, the use of whole tumor cell lysates in tumor immunotherapy would be a very promising approach that can overcome several significant obstacles in vaccine production. Whole tumor cells provide a broad source of tumor-associated antigens and can activate cytotoxic T lymphocytes and CD4+ T helper cells concurrently. On the other hand, as an effective immunotherapy strategy, recent investigations have shown that the multi-targeting of tumor cells with polyclonal antibodies, which are also more effective than monoclonal antibodies at mediating effector functions for target elimination, might minimize the escape variants. Experimental approach: We prepared polyclonal antibodies by immunizing rabbits with the highly invasive 4T1 breast cancer cell line. Findings/Results: In vitro investigation indicated that the immunized rabbit serum inhibited cell proliferation and induced apoptosis in target tumor cells. Moreover, in vivo analysis showed enhanced anti-tumor efficacy of whole tumor cell lysate in combination with tumor cell-immunized serum. This combination therapy proved beneficial in significant inhibition of the tumor growth and the established tumor was entirely eradicated in treated mice. Conclusion and implications: Serial intravenous injections of tumor cell immunized rabbit serum significantly inhibited tumor cell proliferation and induced apoptosis in vitro and in vivo in combination with whole tumor lysate. This platform could be a promising method for developing clinical-grade vaccines and open up the possibility of addressing the effectiveness and safety of cancer vaccines.

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A Review of Monoclonal Antibody-Based Treatments in Non-small Cell Lung Cancer

Cited by 9 publications

References 110 publications

GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins

GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

Enhanced in vivo anti-tumor efficacy of whole tumor lysate in combination with whole tumor cell-specific polyclonal antibody

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