Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

Costa, Ricardo; Czerniecki, Brian J.

doi:10.1038/s41523-020-0153-3

Cited by 128 publications

(108 citation statements)

References 141 publications

(157 reference statements)

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“…Its therapeutic activity against HER2+ breast carcinoma is being evaluated in phase II trials, but also some authors such as Li et al [101] and Jiang et al [5] have showed its efficacy as a targeted therapy for HER2+ gastric and ovarian cancers, respectively. Other examples of anti-HER2 ADCs whose antiproliferative activity is being evaluated in clinical trials for the treatment of HER2+ cancers are ARX788, TAK-522, A116, Tmab Duocarmizine, ALT-P7, DHE50815A, MEDI4276, and Tmab Deruxtecan [89,99,[102][103][104][105]. More information about them, as well as about SYD98 and Tmab deruxtecan [83], can be found in Table 2.…”

Section: Current and Future Situation Of Trastuzumab-based Nanomedicinementioning

confidence: 99%

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Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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HER2 overexpression, which occurs in a fifth of diagnosed breast cancers as well as in other types of solid tumors, has been traditionally linked to greater aggressiveness. Nevertheless, the clinical introduction of trastuzumab has helped to improve HER2-positive patients’ outcomes. As a consequence, nanotechnology has taken advantage of the beneficial effects of the administration of this antibody and has employed it to develop HER2-targeting nanomedicines with promising therapeutic activity and limited toxicity. In this review, the molecular pathways that could be responsible for trastuzumab antitumor activity will be briefly summarized. In addition, since the conjugation strategies that are followed to develop targeting nanomedicines are essential to maintaining their efficacy and tolerability, the ones most employed to decorate drug-loaded nanoparticles and liposomes with trastuzumab will be discussed here. Thus, the advantages and disadvantages of performing this trastuzumab conjugation through adsorption or covalent bindings (through carbodiimide, maleimide, and click-chemistry) will be described, and several examples of targeting nanovehicles developed following these strategies will be commented on. Moreover, conjugation methods employed to synthesized trastuzumab-based antibody drug conjugates (ADCs), among which T-DM1 is well known, will be also examined. Finally, although trastuzumab-decorated nanoparticles and liposomes and trastuzumab-based ADCs have proven to have better selectivity and efficacy than loaded drugs, trastuzumab administration is sometimes related to side toxicities and the apparition of resistances. For this reason also, this review focuses at last on the important role that newer antibodies and peptides are acquiring these days in the development of HER2-targeting nanomedicines.

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Section: Current and Future Situation Of Trastuzumab-based Nanomedicinementioning

confidence: 99%

“…[83],2 [89],3 [99],4 [100],5 [104],6 [105]. AF-HPA: auristatin F-hydroxypropylamide; NSCLC: non-small cell lung carcinoma; PBD-MA: pyrrolo[2,1-c][1,4]benzodiazepine monoamide.…”

mentioning

confidence: 99%

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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“…19 Unlike the other three HERs (HER1, HER3, and HER4), HER2 is highly expressed in many cancer cells, especially in some breast cancers. 20 Moreover, medicines using HER2 as the binding site have been approved by the US FDA for clinical use. 21 Thus, HER2 is considered to be a promising target for theranostic nanomaterials development.…”

Section: Targeting Peptidesmentioning

confidence: 99%

Recent advances on peptide‐based theranostic nanomaterials

Rong

Lei

Zhang

2020

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Theranostic nanomaterial, which amalgamates diagnosis and therapy of diseases into one nanosystem, has become one of the core interests in nanomedicine research. Functional peptides can be integrated into theranostic nanomaterials and endow them with special properties to accomplish much more complicated biomedical tasks. Peptide-based theranostic nanomaterials can be formulated with specific targeting, transmembrane delivery, and stimulus response. In this Minireview, we describe general ideas of fabricating peptide-based theranostic nanomaterials, concerning the design and variegated biomedical applications, and highlighting their advances during the past 5 years.

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“…Monoclonal antibodies are identical Ig produced by clonal immune cells [96]. Although their antitumoral effect is caused by their binding ability and the inhibition of their corresponding receptor, an additional immunological pathway exists for anti-HER2-targeted monoclonal antibodies by which the adaptive and innate immune systems are activated mainly through the antibody-dependent cell-mediated cytotoxicity of natural killer cells and monocytes against tumor cells [97][98][99][100]. Margetuximab, a novel chimeric anti-HER2 IgG1 antibody [101,102], binds to the same receptor and has anti-proliferative effects similar to those of trastuzumab, but it is intended to have a stronger effect on the immune system due to modification of the Fc region.…”

Section: Anti-her2 Targeted Antibody Therapymentioning

confidence: 99%

Clinical Data on Immunotherapy in Breast Cancer

Radosa¹,

Stotz²,

Müller³

et al. 2020

Breast Care

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Background: Breast cancer has traditionally been considered to have a low immunogenic potential compared to other tumor entities. Summary: The most extensively studied immunotherapeutic agents for breast cancer to date are immune checkpoint inhibitors, with the results of the IMpassion130 trial leading to the approval of atezolizumab plus nab-paclitaxel for first-line treatment of programmed cell death ligand 1-positive, metastatic, triple-negative breast cancer, and studies in earlier stages have yielded promising results. Other immunotherapeutic options being assessed in phases 2 and 3 trials include vaccine-based therapies and treatment with anti-human epidermal growth factor receptor 2 (H-directed immune-linked antibodies) and substances evaluated in early clinical trials as cellular therapies (adoptive cell therapy and chimeric antigen receptor T cells). Key Messages: Immunotherapy is an emerging modality for the treatment of breast cancer, as evidenced by the plethora of preclinical and clinical concepts and ongoing trials. Early studies established the role of immunotherapeutic agents in the metastatic setting. Ongoing studies will expand our knowledge about the timing of administration, best partners for combination therapy, and predictive biomarkers to guide immunotherapy for breast cancer.

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Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

Cited by 128 publications

References 141 publications

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Recent advances on peptide‐based theranostic nanomaterials

Clinical Data on Immunotherapy in Breast Cancer

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