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 "title": "Passive immunotherapy",
 "updated": "2026-09-30",
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 "excerpt": "Passive immunotherapy is the administration of pre-made antibodies or immune cells to a patient to prevent or treat disease, used after exposure or for toxins, with protection that is temporary.",
 "snippet": "Passive immunotherapy is the administration of pre-made antibodies or immune cells to a patient to prevent or treat disease, used after exposure or for toxins, with protection that is temporary.",
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 "markdown": "# Passive immunotherapy\n\nPassive immunotherapy is the administration of pre-made antibodies or immune cells to a patient to prevent or treat disease, rather than stimulating the patient's own immune system to make them. It is indicated when a person cannot synthesize antibody, after exposure to a disease they are not immune to, or when a toxin's effects must be neutralized, and it does not induce natural immunity.<sup>[1](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)</sup> Protection is temporary, because the transferred products are eventually cleared.\n\n| Key fact | Value |\n|---|---|\n| Duration of antibody protection | Human IgG circulating half-life about 3 weeks (IgG3, 7 days)<sup>[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC7151993/)</sup> |\n| Palivizumab dosing | 15 mg/kg intramuscularly every 30 days; half-life 17–20 days<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/103770_s5059_lbl.pdf)</sup><sup> • </sup><sup>[4](https://www.ema.europa.eu/en/documents/scientific-discussion/synagis-epar-scientific-discussion_en.pdf)</sup> |\n| Nirsevimab efficacy | 79.5% relative reduction in medically attended RSV lower respiratory tract infection in infants<sup>[5](https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642%2822%2900321-2/abstract)</sup> |\n| Blinatumomab survival benefit | Median overall survival 7.7 vs 4.0 months versus chemotherapy in relapsed/refractory ALL<sup>[6](https://www.medicines.org.uk/emc/product/5064/smpc)</sup> |\n| Lifileucel response rate | Objective response rate 31.4% in pretreated metastatic melanoma<sup>[7](https://www.fda.gov/media/176417/download)</sup> |\n| CAR-T toxicity | CRS in 57–93% of patients and ICANS in 20–70%, depending on the agent<sup>[8](https://ascopubs.org/doi/10.1200/JCO.21.01992)</sup> |\n\n## How it works\n\nTransferred antibodies act through two separable regions. The antigen-binding (Fab) portion neutralizes viruses and toxins by blocking attachment, fusion, and entry into cells.<sup>[9](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1307398/full)</sup> The Fc portion engages Fcγ receptors on immune cells, driving antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis, and complement activation; the same Fc mechanisms can also cause antibody-dependent enhancement, in which non-neutralizing immune complexes worsen disease.<sup>[9](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1307398/full)</sup>\n\nCell-based products supply effector cells rather than antibody. Blinatumomab is an antibody-based T-cell engager rather than an infused cell product: this bispecific antibody links CD19 on B-cell precursor acute lymphoblastic leukemia (ALL) cells to CD3 on the patient's own T cells, and kills through polyclonal T-cell activation that is independent of human leukocyte antigen (HLA) molecules on target cells, so it does not depend on peptide presentation by the cancer.<sup>[6](https://www.medicines.org.uk/emc/product/5064/smpc)</sup> TIL products recognize tumor-specific neoantigens through [T-cell receptor](https://www.edgepedia.org/t-cell-receptor)–peptide HLA engagement and mediate tumor cell lysis; the specific mechanism of action of the approved TIL product lifileucel is stated as unknown in its labeling.<sup>[10](https://www.iovance.com/uploads/Lifileucel-Product-Monograph-English-CA.pdf)</sup> CAR-T cells are gene-therapy products in which T-cell specificity is genetically redirected to a chosen antigen, typically via an antibody-derived recognition domain.<sup>[11](https://www.fda.gov/media/156896/download)</sup>\n\n## How it is done\n\n**Antibody products.** The clinician selects the product class, dose, and route. Pooled IG is given intramuscularly; because maximal serum levels may not occur until about 48 hours after injection, it must be given as soon as possible after exposure.<sup>[1](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)</sup> IVIG replacement in primary immunodeficiency uses about 400–600 mg/kg per month, while immunomodulatory dosing ranges from 1,000 to 3,000 mg/kg, often as 2 g/kg per course divided over five days.<sup>[12](https://www.ncbi.nlm.nih.gov/books/NBK554446/)</sup> RSV monoclonal antibodies are given intramuscularly for prophylaxis only: palivizumab at 15 mg/kg monthly, nirsevimab weight-based (50 mg below 5 kg, 100 mg at or above 5 kg), and clesrovimab as a single fixed 105 mg dose for all infants.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/103770_s5059_lbl.pdf)</sup><sup> • </sup><sup>[13](https://www.cdc.gov/mmwr/volumes/74/wr/mm7432a3.htm)</sup>\n\n**Cell products.** [Blinatumomab](https://www.edgepedia.org/blinatumomab) is given as continuous intravenous infusion cycles of 28 days followed by a 14-day treatment-free interval, with fixed dosing at or above 45 kg body weight and body-surface-area dosing below that.<sup>[14](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125557Orig1s028Correctedlbl.pdf)</sup><sup> • </sup><sup>[15](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=38b482a8-960b-4591-9857-5031ecb830aa)</sup> [Lifileucel](https://www.edgepedia.org/lifileucel), a single infusion of \\( 7.5 \\times 10^{9} \\) to \\( 7.2 \\times 10^{10} \\) viable cells, is preceded by lymphodepletion and followed by aldesleukin.<sup>[7](https://www.fda.gov/media/176417/download)</sup> CAR-T manufacturing requires qualified aseptic processing under current good manufacturing practice and sterility testing, because the final product cannot be filtered or terminally sterilized; fresh products have a limited shelf life with a defined maximum time between formulation and infusion.<sup>[11](https://www.fda.gov/media/156896/download)</sup>\n\n## Origin\n\nSerum therapy for diphtheria and tetanus involves serum from horses immunized with toxins of [Clostridium tetani](https://www.edgepedia.org/clostridium-tetani) and [Corynebacterium diphtheriae](https://www.edgepedia.org/corynebacterium-diphtheriae) neutralizing the toxins.<sup>[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC7151993/)</sup><sup> • </sup><sup>[16](https://journals.asm.org/doi/10.1128/microbiolspec.aid-0026-2014)</sup> The monoclonal era began with the murine anti-CD3 antibody OKT3 (muromonab), approved in 1986 for prevention of organ transplant rejection, and progressed through chimeric and humanized antibodies to adalimumab (Humira), the first IgG with a completely human sequence origin, approved in 2002.<sup>[16](https://journals.asm.org/doi/10.1128/microbiolspec.aid-0026-2014)</sup><sup> • </sup><sup>[17](https://application.wiley-vch.de/books/sample/3527329374_c01.pdf)</sup> For RSV, RSV-IGIV (RespiGam) was approved in January 1996 and palivizumab (Synagis) in mid-1998.<sup>[18](https://link.springer.com/article/10.1186/1471-2334-9-106)</sup> The term \"adoptive cell transfer\" entered the literature, and TIL therapy was clinically developed for melanoma at the [National Cancer Institute](https://www.edgepedia.org/national-cancer-institute) in the late 1980s; first-generation CAR designs combining an antibody-derived single-chain variable fragment with CD3ζ signaling were described in 1993.<sup>[19](https://doi.org/10.1016/j.ymthe.2025.03.005)</sup>\n\n## Variants\n\nThe main product classes are: pooled human immunoglobulin given intramuscularly, intravenously, or subcutaneously; hyperimmune globulins from vaccinated or convalescent donors, used for postexposure prophylaxis in specific situations, including rabies; specific equine antitoxins such as botulinum and diphtheria antitoxin; recombinant monoclonal antibodies such as palivizumab and nirsevimab; bispecific T-cell engagers such as blinatumomab; and autologous cell products including CAR-T and TIL.<sup>[1](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)</sup><sup> • </sup><sup>[12](https://www.ncbi.nlm.nih.gov/books/NBK554446/)</sup><sup> • </sup><sup>[11](https://www.fda.gov/media/156896/download)</sup> [Palivizumab](https://www.edgepedia.org/palivizumab) is a humanized IgG1κ antibody with 95% human and 5% murine sequences directed at an epitope in antigenic site A of the RSV F protein.<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/103770_s5059_lbl.pdf)</sup>\n\n## Applications\n\n**Timing matters.** [Diphtheria](https://www.edgepedia.org/diphtheria) antitoxin started on day 1 of disease gave 0% mortality (n = 183); delaying to days 2, 3, and 4 raised case-fatality to 1.6% (n = 905), 4.4% (n = 632), and 6.9% (n = 436).<sup>[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC7151993/)</sup> For severe respiratory viral infections, passive immunotherapy is most effective within 4–5 days of symptom onset.<sup>[9](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1307398/full)</sup>\n\n**RSV prophylaxis.** Palivizumab reduced RSV hospitalization by 55% in the pivotal trial (4.8% vs 10.6%, p < 0.001) and by 45% in children with congenital heart disease (5.3% vs 9.7%, p = 0.003).<sup>[3](https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/103770_s5059_lbl.pdf)</sup><sup> • </sup><sup>[4](https://www.ema.europa.eu/en/documents/scientific-discussion/synagis-epar-scientific-discussion_en.pdf)</sup> A meta-analysis of six trials (2,196 children) found an overall relative risk of RSV hospitalization of 0.53, with a significant reduction in ICU admission (RR 0.29) but no significant reduction in mechanical ventilation or mortality.<sup>[18](https://link.springer.com/article/10.1186/1471-2334-9-106)</sup> Nirsevimab reduced medically attended RSV lower respiratory tract infection by 79.5% (95% CI 65.9–87.7), hospital admission by 77.3%, and very severe disease by 86.0%.<sup>[5](https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642%2822%2900321-2/abstract)</sup> In June 2025 the FDA licensed clesrovimab (Enflonsia), a second long-acting RSV monoclonal antibody, and ACIP recommended it on June 26, 2025 as an alternative to nirsevimab for infants under 8 months entering their first RSV season; since 2023, ACIP has recommended that all infants be protected through one of three products, maternal RSV vaccination (Abrysvo), nirsevimab, or clesrovimab, with no single product preferred.<sup>[13](https://www.cdc.gov/mmwr/volumes/74/wr/mm7432a3.htm)</sup> Treatment of established disease fails: in 420 infants with existing RSV bronchiolitis, intravenous palivizumab was not superior to placebo (readmission 11% vs 9.3%, p = 0.51).<sup>[20](https://publications.aap.org/pediatrics/article/143/3/e20182308/37270/Monoclonal-Antibody-Treatment-of-RSV-Bronchiolitis)</sup>\n\n**COVID-19.** An individual participant data meta-analysis of six randomized trials (3,079 hospitalized patients) found no significant improvement in sustained recovery overall, but a benefit in seronegative patients (rate ratio 1.16, 95% CI 1.04–1.29) that was absent in seropositive patients (interaction p = 0.02).<sup>[21](https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1004616)</sup> With new [SARS-CoV-2](https://www.edgepedia.org/sars-cov-2) variants and high population seropositivity, passive immunotherapy currently has a limited role in COVID-19 management, though it will likely be important again in early stages of future viral outbreaks.<sup>[22](https://pmc.ncbi.nlm.nih.gov/articles/PMC12068974/)</sup>\n\n**Oncology.** Blinatumomab extended median overall survival to 7.7 months (95% CI 5.6–9.6) versus 4.0 months (95% CI 2.9–5.3) with standard chemotherapy in relapsed/refractory ALL (HR 0.71, p = 0.012).<sup>[6](https://www.medicines.org.uk/emc/product/5064/smpc)</sup> Lifileucel achieved an objective response rate of 31.4% (95% CI 24.1–39.4%) in a pooled set of 153 patients, with complete responses in 5.2%.<sup>[7](https://www.fda.gov/media/176417/download)</sup><sup> • </sup><sup>[23](https://aacrjournals.org/clincancerres/article/31/19/4004/765498/FDA-Approval-Summary-Lifileucel-for-Unresectable)</sup> On February 16, 2024, the FDA granted accelerated approval to lifileucel (Amtagvi), the first tumor-derived T-cell therapy it has approved.<sup>[23](https://aacrjournals.org/clincancerres/article/31/19/4004/765498/FDA-Approval-Summary-Lifileucel-for-Unresectable)</sup>\n\n## Limitations and alternatives\n\n**Antibody products.** IVIG can cause fever, chills, headache, and volume overload, with rare serious effects including anaphylaxis, kidney impairment, thrombosis, aseptic meningitis, hemolytic anemia, and transfusion-related acute lung injury; subcutaneous administration produces fewer systemic effects.<sup>[1](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)</sup> Antibody content against specific agents varies by as much as 10-fold among IG preparations.<sup>[1](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)</sup> The Fc-mediated enhancement risk is not hypothetical: a formalin-inactivated RSV vaccine of the 1960s caused enhanced respiratory disease through non-neutralizing immune complexes, fatal in two children.<sup>[9](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1307398/full)</sup>\n\n**Cell products.** CRS after CAR-T therapy ranges from 57% to 93% and ICANS from 20% to 70% by agent.<sup>[8](https://ascopubs.org/doi/10.1200/JCO.21.01992)</sup><sup> • </sup><sup>[24](https://www.mdpi.com/2072-6644/17/2/282)</sup> Mechanistically, Margherita Norelli and colleagues showed in [Nature Medicine](https://www.edgepedia.org/nature-medicine) in 2018 that monocyte-derived IL-1 and IL-6 are differentially required for CRS and neurotoxicity,<sup>[25](https://doi.org/10.1038/s41591-018-0036-4)</sup> and Theodoros Giavridis and colleagues showed in Nature Medicine in 2018 that macrophage-mediated IL-1 signaling drives CRS.<sup>[26](https://doi.org/10.1038/s41591-018-0041-7)</sup> Management uses tocilizumab with or without corticosteroids for severe CRS, and corticosteroids for moderate to severe ICANS; tocilizumab does not resolve ICANS and may worsen it, because it does not cross the blood-brain barrier and transiently raises IL-6 in serum and cerebrospinal fluid.<sup>[8](https://ascopubs.org/doi/10.1200/JCO.21.01992)</sup><sup> • </sup><sup>[27](https://link.springer.com/article/10.1007/s10555-024-10227-1)</sup> Robert Q. Le and colleagues described in The Oncologist in 2018 the FDA approval of tocilizumab for severe or life-threatening CAR T cell-induced CRS,<sup>[28](https://doi.org/10.1634/theoncologist.2018-0028)</sup> and the REMS for CAR-T products requires at least two doses of tocilizumab available per patient, administrable within two hours of infusion.<sup>[29](https://www.ncbi.nlm.nih.gov/books/NBK592426/)</sup> CD19-directed CAR-T causes prolonged B-cell aplasia and hypogammaglobulinemia lasting up to 5 years, managed with IgG replacement.<sup>[29](https://www.ncbi.nlm.nih.gov/books/NBK592426/)</sup><sup> • </sup><sup>[27](https://link.springer.com/article/10.1007/s10555-024-10227-1)</sup> New T-cell malignancies after CAR-T therapy have been reported but are exceedingly rare, and patients are monitored for second malignancies indefinitely.<sup>[30](https://www.nature.com/articles/s41571-024-00903-0)</sup> Published sources do not quantify head-to-head comparisons with active vaccination, small-molecule antivirals, or targeted small-molecule cancer therapy.\n\n## References\n\n1. [Passive Immunization - Merck Manual Professional Edition](https://www.merckmanuals.com/professional/infectious-diseases/immunization/passive-immunization)\n2. [Passive Immunization (book chapter)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7151993/)\n3. [SYNAGIS (PALIVIZUMAB) FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/103770_s5059_lbl.pdf)\n4. [Synagis EPAR Scientific Discussion (EMA)](https://www.ema.europa.eu/en/documents/scientific-discussion/synagis-epar-scientific-discussion_en.pdf)\n5. [abstract (thelancet.com)](https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642%2822%2900321-2/abstract)\n6. [BLINCYTO 38.5 micrograms SmPC (European Summary of Product Characteristics)](https://www.medicines.org.uk/emc/product/5064/smpc)\n7. [AMTAGVI (lifileucel) FDA prescribing information, 2024](https://www.fda.gov/media/176417/download)\n8. [Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline](https://ascopubs.org/doi/10.1200/JCO.21.01992)\n9. [Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy – a balancing act](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1307398/full)\n10. [AMTAGVI (lifileucel) Health Canada Product Monograph](https://www.iovance.com/uploads/Lifileucel-Product-Monograph-English-CA.pdf)\n11. [Considerations for the Development of Chimeric Antigen Receptor T Cell Products; Guidance for Industry](https://www.fda.gov/media/156896/download)\n12. [Intravenous Immunoglobulin (IVIG) - StatPearls](https://www.ncbi.nlm.nih.gov/books/NBK554446/)\n13. [Use of Clesrovimab for Prevention of Severe RSV–Associated Lower Respiratory Tract Infections in Infants: Recommendations of ACIP, United States, 2025](https://www.cdc.gov/mmwr/volumes/74/wr/mm7432a3.htm)\n14. [BLINCYTO (blinatumomab) FDA prescribing information, 2024](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125557Orig1s028Correctedlbl.pdf)\n15. [BLINCYTO label (DailyMed, revised 2025-2026)](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=38b482a8-960b-4591-9857-5031ecb830aa)\n16. [History and Practice: Antibodies in Infectious Diseases](https://journals.asm.org/doi/10.1128/microbiolspec.aid-0026-2014)\n17. [Therapeutic Antibodies – from Past to Future (book chapter)](https://application.wiley-vch.de/books/sample/3527329374_c01.pdf)\n18. [A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection (BMC Infectious Diseases)](https://link.springer.com/article/10.1186/1471-2334-9-106)\n19. [From concept to cure: The evolution of CAR-T cell therapy (Molecular Therapy, 2025)](https://doi.org/10.1016/j.ymthe.2025.03.005)\n20. [Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial (Pediatrics)](https://publications.aap.org/pediatrics/article/143/3/e20182308/37270/Monoclonal-Antibody-Treatment-of-RSV-Bronchiolitis)\n21. [Passive immunotherapy for adults hospitalized with COVID-19: An individual participant data meta-analysis of six randomized controlled trials (PLOS Medicine)](https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1004616)\n22. [Long-term outcomes of passive immunotherapy for COVID-19: pooled analysis of the ACTIV-3/TICO platform randomized clinical trial](https://pmc.ncbi.nlm.nih.gov/articles/PMC12068974/)\n23. [FDA Approval Summary: Lifileucel for Unresectable or Metastatic Melanoma Previously Treated with an Anti–PD-1–Based Immunotherapy (Clinical Cancer Research, 2025)](https://aacrjournals.org/clincancerres/article/31/19/4004/765498/FDA-Approval-Summary-Lifileucel-for-Unresectable)\n24. [Comprehensive Review of Early and Late Toxicities in CAR T-Cell Therapy and Bispecific Antibody Treatments for Hematologic Malignancies (Cancers)](https://www.mdpi.com/2072-6644/17/2/282)\n25. [Margherita Norelli and colleagues (2018). Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature Medicine.](https://doi.org/10.1038/s41591-018-0036-4)\n26. [Theodoros Giavridis and colleagues (2018). CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nature Medicine.](https://doi.org/10.1038/s41591-018-0041-7)\n27. [Evolving strategies for addressing CAR T-cell toxicities (Cancer and Metastasis Reviews, 2024)](https://link.springer.com/article/10.1007/s10555-024-10227-1)\n28. [Robert Q. Le and colleagues (2018). FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. The Oncologist.](https://doi.org/10.1634/theoncologist.2018-0028)\n29. [CART Cell Therapy Toxicity (StatPearls)](https://www.ncbi.nlm.nih.gov/books/NBK592426/)\n30. [Current understanding and management of CAR T cell-associated toxicities | Nature Reviews Clinical Oncology](https://www.nature.com/articles/s41571-024-00903-0)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Biologics, monoclonal antibodies, and biosimilars*\n\n*Initially written Sep 29, 2026 · Reviewed: Sep 30, 2026 · Edited: Sep 30, 2026 · Last review: Sep 30, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n",
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 "credit_md": "\"[Passive immunotherapy](https://www.edgepedia.org/passive-immunotherapy)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/passive-immunotherapy](https://www.edgepedia.org/passive-immunotherapy). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).",
 "credit_html": "\"<a href=\"https://www.edgepedia.org/passive-immunotherapy\">Passive immunotherapy</a>\", Edgepedia (EdgeChat), <a href=\"https://www.edgepedia.org/passive-immunotherapy\">https://www.edgepedia.org/passive-immunotherapy</a>. <a href=\"https://www.edgepedia.org/edgepedia/license\">Edgepedia Community License 1.0</a>.",
 "speakable": "Passive immunotherapy is the administration of pre-made antibodies or immune cells to a patient to prevent or treat disease, used after exposure or for toxins, with protection that is temporary."
}
