Antibodies to watch in 2024

Crescioli, Silvia; Kaplon, Hélène; Chenoweth, Alicia; Wang, Lin; Visweswaraiah, Jyothsna; Reichert, Janice M.

doi:10.1080/19420862.2023.2297450

Cited by 57 publications

(15 citation statements)

References 52 publications

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“…To date, the asymmetric 1 + 1 TCEs odronextamab (CD20/CD3ε) 80 and linvoseltamab (BCMA/CD3ε) based on Regeneron’s VelociBi technology are currently under regulatory review that may result in approval in 2024, and various additional TCEs are in advanced clinical development in NHL, multiple myeloma and AML. 75 Importantly, emerging data support the idea that TCEs may in the future also find broader application in solid tumors. In fact, recently promising clinical data have been published for Amgen’s 1 + 1 DLL3/CD3ε Fc-BiTE tarlatamab for the treatment of R/R small cell lung cancer, 81 , 82 which is currently under regulatory review, and for Xencor/Amgen’s 2 + 1 STEAP1/CD3ε XmAb xaluritamig for the treatment of R/R prostate cancer.…”

Section: Outlook For the Futurementioning

confidence: 91%

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A pivotal decade for bispecific antibodies?

Surowka,

Klein

2024

mAbs

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Bispecific antibodies (bsAbs) are a class of antibodies that can mediate novel mechanisms of action compared to monospecific monoclonal antibodies (mAbs). Since the discovery of mAbs and their adoption as therapeutic agents in the 1980s and 1990s, the development of bsAbs has held substantial appeal. Nevertheless, only three bsAbs (catumaxomab, blinatumomab, emicizumab) were approved through the end of 2020. However, since then, 11 bsAbs received regulatory agency approvals, of which nine (amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) were approved for the treatment of cancer and two (faricimab, ozoralizumab) in non-oncology indications. Notably, of the 13 currently approved bsAbs, two, emicizumab and faricimab, have achieved blockbuster status, showing the promise of this novel class of therapeutics. In the 2020s, the approval of additional bsAbs can be expected in hematological malignancies, solid tumors and non-oncology indications, establishing bsAbs as essential part of the therapeutic armamentarium.

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Section: Outlook For the Futurementioning

confidence: 91%

“…Notably, the dual-targeted PD-1/VEGF inhibitory bsAb ivonescimab is currently under regulatory review by the National Medicinal Product Administration in China for treatment of NSCLC. 75 , 95 …”

Section: Outlook For the Futurementioning

confidence: 99%

A pivotal decade for bispecific antibodies?

Surowka,

Klein

2024

mAbs

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“…Currently, many BsAbs are being analyzed, and some of them are already in the final phase of clinical trials or have achieved registration. Examples of such antibodies include bintrafusp alfa, erfonrilimab, linvoseltamab, and zanidatamab [57][58][59].…”

Section: Investigational Bispecific Antibodiesmentioning

confidence: 99%

“…Erfonrilimab acts on the immune checkpoint proteins PD-L1 and cytotoxic T lymphocyte antigen 4 (CTLA-4), allowing it to modulate the immune response to cancer cells by enhancing the activity of T lymphocytes. Research is being conducted to evaluate the effectiveness, safety, and tolerance of erfonrilimab in combination with first-line chemotherapy for patients with non-small cell lung cancer [58].…”

Section: Investigational Bispecific Antibodiesmentioning

confidence: 99%

Double hit — bispecific antibodies in cancer therapy

Bogdanowicz,

Wojas-Krawczyk,

Krzyżanowska

et al. 2024

Oncol Clin Pract

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Immunotherapy has emerged as a promising strategy for cancer treatment, with bispecific antibodies (BsAbs) demonstrating significant therapeutic potential. BsAbs are biological molecules capable of simultaneously binding to two distinct antigens, allowing the immune response to target cancer cells precisely. However, despite promising results in preclinical studies and early clinical trials, immunotherapy based on these antibodies faces several significant issues that require careful consideration. One of them is the development of therapy resistance, which often leads to a loss of treatment effectiveness. Another challenge is the associated toxicity of immunotherapy. While BsAbs are designed to limit adverse effects, there remains a risk of side effects that can impact the quality of life for patients. Furthermore, it should be noted that the production of BsAbs is burdened with significant costs and involves complex processes, negatively affecting the accessibility of this therapy for the majority of patients. Hence, continuous efforts are necessary to develop more efficient and cost-effective methods for producing these antibodies to enable a broader range of patients to benefit from this innovative therapy.

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“…Monoclonal antibodies are used successfully in all major therapy areas due to their exquisite specificity and low intrinsic toxicity. 1 Despite the progress made, drug attrition, which is partly due to target-related uncertainties, remains an issue. 2 This is especially relevant in the case of antibody-drug conjugates (ADCs) where toxicity remains the dose-limiting factor.…”

Section: Introductionmentioning

confidence: 99%

Application of quantitative protein mass spectrometric data in the early predictive analysis of membrane-bound target engagement by monoclonal antibodies

Sepp,

Muliaditan

2024

mAbs

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Model-informed drug discovery advocates the use of mathematical modeling and simulation for improved efficacy in drug discovery. In the case of monoclonal antibodies (mAbs) against cell membrane antigens, this requires quantitative insight into the target tissue concentration levels. Protein mass spectrometry data are often available but the values are expressed in relative, rather than in molar concentration units that are easier to incorporate into pharmacokinetic models. Here, we present an empirical correlation that converts the parts per million (ppm) concentrations in the PaxDb database to their molar equivalents that are more suitable for pharmacokinetic modeling. We evaluate the insight afforded to target tissue distribution by analyzing the likely tumor-targeting accuracy of mAbs recognizing either epidermal growth factor receptor or its homolog HER2. Surprisingly, the predicted tissue concentrations of both these targets exceed the Kd values of their respective therapeutic mAbs. Physiologically based pharmacokinetic (PBPK) modeling indicates that in these conditions only about 0.05% of the dosed mAb is likely to reach the solid tumor target cells. The rest of the dose is eliminated in healthy tissues via both nonspecific and target-mediated processes. The presented approach allows evaluation of the interplay between the target expression level in different tissues that determines the overall pharmacokinetic properties of the drug and the fraction that reaches the cells of interest. This methodology can help to evaluate the efficacy and safety properties of novel drugs, especially if the off-target cell degradation has cytotoxic outcomes, as in the case of antibody-drug conjugates.

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Antibodies to watch in 2024

Cited by 57 publications

References 52 publications

A pivotal decade for bispecific antibodies?

A pivotal decade for bispecific antibodies?

Double hit — bispecific antibodies in cancer therapy

Application of quantitative protein mass spectrometric data in the early predictive analysis of membrane-bound target engagement by monoclonal antibodies

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