Thymosin Alpha-1

At a glance

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Thymosin alpha-1 vs. TB-500: completely different molecules

Thymosin alpha-1 and TB-500 (thymosin beta-4) are from different protein families, have different structures, different mechanisms, and different evidence bases. The only thing they share is the word "thymosin" and their origin in thymus tissue.

The thymosin family contains dozens of peptides originally isolated from thymus tissue. They were named alphabetically based on their isoelectric point during initial characterization. The alpha and beta subfamilies turned out to be entirely unrelated proteins that happen to share a name.

Thymosin alpha-1 is a 28-amino-acid immunomodulatory peptide that works through dendritic cell activation and T-cell maturation. It has 30+ clinical trials, is approved in 35+ countries, and has a decades-long safety record.

TB-500 is a 7-amino-acid synthetic fragment of thymosin beta-4, a 43-amino-acid actin-binding protein involved in wound healing and tissue repair. It has zero human clinical trials for the fragment itself.

Here is why this distinction matters:

• Different families: Alpha-1 modulates the immune system. Beta-4 regulates actin and cell migration.
• Different evidence: Alpha-1 has multiple RCTs and meta-analyses. TB-500 has zero human trials.
• Different regulatory paths: Alpha-1 is an approved pharmaceutical in 35+ countries. TB-500 is a research compound everywhere.
• Different mechanisms: Alpha-1 works through TLR signaling and dendritic cell maturation. TB-500 works through actin sequestration.
• Not interchangeable: Taking one does not replicate the effects of the other.

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What is thymosin alpha-1?

Thymosin alpha-1 is a peptide hormone naturally produced by the thymus gland — the small organ behind your sternum that trains immune cells during childhood and adolescence. Ta1 is cleaved from a larger precursor protein called prothymosin alpha (113 amino acids) and plays a central role in immune regulation.

The peptide was first isolated and sequenced by Allan Goldstein and colleagues at the University of Texas Medical Branch in 1977.^[1] They extracted it from "thymosin fraction 5," a partially purified thymic preparation that had already shown immune-boosting effects in early clinical studies for immunodeficiency disorders.

The synthetic version — thymalfasin — is chemically identical to the naturally occurring peptide and was developed for clinical use in the 1980s and 1990s. It is marketed as Zadaxin by SciClone Pharmaceuticals (taken private by a consortium led by GL Capital in 2017) and is approved in over 35 countries across Asia, Latin America, Eastern Europe, and the Middle East.

Ta1 is not a growth factor, a hormone in the traditional sense, or a performance-enhancing peptide. It is an immune modulator — it tunes the immune system rather than simply boosting or suppressing it. This bidirectional activity is one of its most interesting properties: it can enhance immune responses in immunocompromised patients while also promoting tolerance in autoimmune contexts.

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How it works

In plain terms, thymosin alpha-1 activates the immune system's "first responder" cells — dendritic cells — which then coordinate the broader immune response. Think of dendritic cells as generals who receive intelligence (about pathogens or cancer cells) and issue orders to the infantry (T-cells and NK cells). Ta1 makes these generals more effective at both gathering intelligence and issuing orders.^[2]

Detailed mechanism (for advanced readers)

Thymosin alpha-1's mechanism operates through several established pathways:

• Toll-like receptor (TLR) signaling (primary mechanism): Ta1 acts as an endogenous ligand for TLR2, TLR3, TLR4, TLR7, and TLR9 on dendritic cells and other antigen-presenting cells. This activates downstream signaling through MyD88-dependent and IRF3-dependent pathways, triggering NF-kB and p38 MAPK cascades.^[3]
• Dendritic cell maturation: Ta1 promotes the functional maturation of dendritic cells, increasing their antigen-presenting capacity and IL-12 production. Mature DCs then drive Th1 polarization of the adaptive immune response.^[3]
• T-cell differentiation: Promotes maturation and differentiation of T-lymphocytes. Increases CD4+, CD8+, and CD3+ cell counts, particularly in immunocompromised patients where these are depleted.
• NK cell enhancement: Increases natural killer cell activity and cytotoxicity against virus-infected and tumor cells.
• Cytokine modulation: Increases production of IFN-gamma, IL-2, IL-3, and IL-12 while modulating pro-inflammatory cytokines. This is a tuning effect, not a simple upregulation.
• Macrophage polarization: In tumor microenvironments, Ta1 promotes M2-to-M1 macrophage polarization, reversing the immunosuppressive state that tumors create to evade immune detection.^[16]

Two 2026 primary studies add possible mechanisms, but remain preclinical: one reported neuroprotection in cell and mouse stroke models through HCRTR1/RIPK3 signaling, and another reported improved chemotherapy-associated antitumor immunity in mouse models through dendritic-cell TLR7 signaling.^[24][25] Neither tested Ta1 as a treatment in people, so these findings do not establish benefit for stroke or cancer.

How it differs from related compounds:

• vs. TB-500 / Thymosin beta-4: Completely different protein family and mechanism. TB-500 works through actin regulation and cell migration for tissue repair. Ta1 works through immune cell activation and TLR signaling. They are not substitutes for each other.
• vs. BPC-157: BPC-157 primarily promotes tissue repair through angiogenesis and growth factor signaling. Ta1 primarily modulates immune function. Mechanistically complementary but targeting different systems.
• vs. Thymulin: Another thymic peptide (a nonapeptide requiring zinc), but with a narrower mechanism focused on T-cell maturation. Ta1 has broader immune-modulatory activity.

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What the research says

Thymosin alpha-1 has been studied in over 30 clinical trials involving more than 11,000 subjects. For a peptide unavailable in the US, this is an extraordinarily deep evidence base. The quality varies — many studies come from Chinese hospitals — but the volume is substantial.

Research timeline

Hepatitis B and C trials

Hepatitis B has the most direct trial data for thymosin alpha-1, but that does not establish clinical benefit. An updated Cochrane review identified 10 randomized trials (1,349 participants) and judged the evidence low certainty for serious adverse events and very low certainty for mortality, liver-related outcomes, quality of life, and histological improvement.^[8] The older trials below are useful context for the earlier virological-response signal, but their limitations matter when interpreting it.

Sepsis trials

Sepsis was long considered thymosin alpha-1's most promising clinical use — but the largest and most rigorous trial was negative.^[22] Earlier, smaller meta-analyses had pointed in a more favorable direction, so it is worth seeing how the picture changed:

The rationale for Ta1 in sepsis is biologically appealing: sepsis causes "immunoparalysis" — a state where the immune system becomes so overwhelmed that it essentially shuts down. Ta1's ability to restore dendritic cell function and T-cell counts addresses this directly. Expert consensus documents in some countries had recommended Ta1 for sepsis treatment — but those recommendations predate TESTS, whose clearly null result should now temper them.

The earlier positive signal came largely from modestly sized, predominantly single-centre Chinese ICU trials. TESTS — larger and more rigorous than all of them combined — did not reproduce that benefit, so on current evidence Ta1 does not support routine use in sepsis.

COVID-19 trials

The COVID-19 pandemic generated significant interest in Ta1 as an immune modulator, with multiple studies published:

Cancer adjunct studies

A September 2026 scoping review mapped 26 cancer publications, predominantly retrospective studies and case reports. Heterogeneity and inconsistent harms reporting limit conclusions; a severe combination-treatment toxicity case did not establish Ta1-specific causality.^[26]

Thymosin alpha-1 has been studied as an immunotherapy adjunct in several cancers, particularly hepatocellular carcinoma (HCC), melanoma, and non-small cell lung cancer (NSCLC):

• Hepatocellular carcinoma: Multiple studies show improved outcomes when Ta1 is combined with chemoembolization (TACE). FDA granted orphan drug designation for HCC.^[17]
• Melanoma: Phase II trials show Ta1 may enhance the effect of CTLA-4 inhibitors. FDA granted orphan drug designation for melanoma.^[16]
• NSCLC: Studies of Ta1 combined with chemotherapy show trends toward improved survival and immune reconstitution.

The mechanism — promoting M2-to-M1 macrophage polarization and restoring anti-tumor immune function — is well-supported. But large-scale Phase III data is limited, and Ta1 has not been approved for any cancer indication in any country.

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What the evidence shows

People come to thymosin alpha-1 with specific questions. Here's what the published research actually tells us about the most common areas of interest:

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Safety & side effects

What research shows

Thymosin alpha-1 has one of the most extensively documented safety profiles of any peptide — with decades of international clinical use. That experience does not establish safety in every indication, combination or formulation.

An older 2024 review reported no serious adverse events attributed to Ta1 in its included trials. That historical summary does not establish comprehensive safety.^[18] Animal toxicology studies using subcutaneous injections in mice, rats, and marmosets over 13-26 weeks at doses up to 800 times the clinical dose found no drug-related adverse effects.

Commonly reported side effects

Based on clinical trial data and decades of post-marketing surveillance:

• Injection-site reactions: Redness, mild pain, or irritation at the injection site (most common, usually mild)
• Fever: Mild, typically when combined with interferon therapy
• Fatigue: Occasional, usually transient
• Muscle aches: Rare, more common in combination therapy
• Nausea: Rare, more common at higher doses

Reported side effects are often mild, but incomplete harms reporting prevents a broad claim of superior safety to other immunomodulators.

Contraindications

Contraindications and interactions

Established contraindications:

• Organ transplant recipients: Ta1's immunomodulatory action could potentially trigger graft rejection. This is the one well-established contraindication.
• Pregnancy and breastfeeding: Insufficient safety data for these populations.

Theoretical considerations:

• Active autoimmune disease: Ta1 is an immune modulator, not a pure stimulant — some research suggests it may actually promote immune tolerance. However, caution is warranted in active autoimmune flares.
• Immunosuppressive therapy: Potential interaction with immunosuppressant medications. Consult your prescribing physician.

Drug interactions: No formal interaction studies beyond combination trials with interferon and chemotherapy agents. No significant interactions have been identified in decades of clinical use.

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How people use it

In the 35+ countries where thymosin alpha-1 is approved, it is prescribed as a pharmaceutical product (Zadaxin) with standardized dosing. In the US, where it is not approved, access has been through compounding pharmacies (when permitted) or research channels.

Administration

• Subcutaneous injection is the standard route in all clinical trials and approved formulations
• Dosing in clinical trials: Most trials used 1.6 mg subcutaneously twice weekly — this is the standard pharmaceutical dose for Zadaxin
• Treatment duration: Varies by indication — typically 6 months for hepatitis B, 2-4 weeks for sepsis

Clinical contexts

In countries where Ta1 is approved, common clinical uses include:

• Chronic hepatitis B — as monotherapy or combination with antivirals
• Vaccine adjuvant — approved in Italy to enhance influenza vaccine response in immunocompromised elderly patients
• Cancer adjunct — combined with chemotherapy or immunotherapy in HCC, melanoma, and NSCLC
• Sepsis — in ICU settings to restore immune function during immunoparalysis
• General immune support — in immunocompromised patients (HIV, post-chemotherapy)

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Legal & regulatory status

As of August 2026:

Thymosin alpha-1 has one of the most complex regulatory stories in the peptide space — approved internationally as a pharmaceutical but caught in regulatory limbo in the US.

International approvals

Thymalfasin (Zadaxin) is approved in over 35 countries including China, India, Italy, Brazil, Argentina, South Korea, Philippines, and many countries across Latin America, Eastern Europe, and the Middle East. It is approved for:

• Chronic hepatitis B treatment
• Chronic hepatitis C (combination therapy)
• Immune adjuvant for vaccines (Italy)
• General immune enhancement in immunocompromised patients

FDA status (United States)

Thymosin alpha-1 is not FDA-approved for any indication. The FDA has granted orphan drug designations for:

• Chronic active hepatitis B
• Hepatocellular carcinoma
• Malignant melanoma
• DiGeorge syndrome (immune deficiency)

Orphan drug designation is not the same as approval — it provides development incentives but does not authorize marketing.

In September 2024, the FDA removed Ta1 from the Category 2 restricted list after the nominator withdrew the substance. On December 4, 2024, the Pharmacy Compounding Advisory Committee (PCAC) voted against including Ta1 on the 503A bulks list — recommending against compounding.^[20]

Ta1 has stayed in that position since. FDA's bulk-substance page, which the agency restructured on April 22, 2026 into an active Category 2 table and a separate "nominated but withdrawn" table, lists Ta1 in the second one — and still publishes a safety-risk finding for it. Ta1 was not on the July 2026 PCAC agenda and is not named in reporting on the further peptide meeting FDA is said to have signalled.

WADA / anti-doping status

Thymosin alpha-1 is not explicitly named on the WADA Prohibited List. This is in contrast to thymosin beta-4 and its derivatives (including TB-500), which are specifically prohibited under S2.3 (Growth Factors and Growth Factor Modulators). Ta1 may theoretically fall under the broad "other growth factors" clause, but its status is ambiguous. Athletes considering Ta1 should seek specific guidance from their sport's anti-doping authority.^[21]

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Related content

Guide

How to Reconstitute Peptides

A clear, safety-first guide to preparing lyophilized peptides. Essential reading if you're working with thymosin alpha-1.

Peptide

TB-500 Profile

The most commonly confused sibling. TB-500 is from the thymosin BETA family — different protein, different mechanism, different evidence base.

Peptide

BPC-157 Profile

Another popular peptide in the healing and immune space. Compare BPC-157's tissue repair focus with Ta1's immune modulation.

News

Correction: The Kennedy Peptide Reclassification Story

Why we retracted the February 2026 reclassification story that named Thymosin Alpha-1, and what the record actually shows.

Tool

Reconstitution Calculator

Calculate exact syringe units for Thymosin Alpha-1 preparation.

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References

1. [1]

   Goldstein AL, Low TL, McAdoo M, et al.. “Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide.” Proc Natl Acad Sci USA. 1977. 74(2):725–729 DOI PubMedAnimal study

   Foundational paper — first isolation and sequence characterization of thymosin alpha-1 from calf thymus tissue.

2. [2]

   Romani L, Bistoni F, Montagnoli C, et al.. “Thymosin alpha 1: an endogenous regulator of inflammation, immunity, and tolerance.” Ann N Y Acad Sci. 2007. 1112:326–338 DOI PubMedReview

   Authoritative review of Ta1 mechanism — covers DC maturation, TLR signaling, and immune tolerance induction.

3. [3]

   Romani L, Bistoni F, Perruccio K, et al.. “Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling.” Blood. 2004. 103(11):4232–4239 DOI PubMedAnimal study

   Key mechanistic paper demonstrating Ta1 activates DCs via TLR2/TLR9, MyD88-dependent pathway, and p38 MAPK/NF-kB signaling.

4. [4]

   Garaci E. “Thymosin alpha 1: a historical overview.” Ann N Y Acad Sci. 2007. 1112:14–20 DOI PubMedReview

   Comprehensive historical overview by a leading Ta1 researcher covering discovery, development, and clinical applications.

5. [5]

   Chien RN, Liaw YF, Chen TC, Yeh CT, Sheen IS. “Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial.” Hepatology. 1998. 27(5):1383–1387 DOI PubMedRCT

   Key RCT demonstrating 40.6% virological response vs 9.4% control. Taiwanese study with adequate randomization.

6. [6]

   Chan HL, Tang JL, Tam W, Sung JJ. “The efficacy of thymosin in the treatment of chronic hepatitis B virus infection: a meta-analysis.” Aliment Pharmacol Ther. 2001. 15(12):1899–1905 DOI PubMedSystematic review

   Meta-analysis of 5 RCTs (353 patients). Showed 3-fold superiority over placebo. Limited by small total sample size and variable trial quality.

7. [7]

   You J, Zhuang L, Tang BZ, et al.. “Thymosin-alpha1 for people with chronic hepatitis B.” Cochrane Database Syst Rev. 2006. 2022(3):CD006446 DOISystematic review

   Historical HBV review reporting virological-response signals. It does not establish current clinical benefit; see the 2026 Cochrane update and its low/very-low outcome certainty.

8. [8]

   Naing C, Ni H, Aung HH, et al.. “Thymosin-α1 for people with chronic hepatitis B.” Cochrane Database Syst Rev. 2026. 9(9):CD014610 DOI PubMedSystematic review

   Updated Cochrane review of 10 RCTs (1,349 participants). Pooled estimates were limited by bias concerns, imprecision, and inconsistency; certainty was low for serious adverse events and very low for other key outcomes.

9. [9]

   Sherman KE, Sjogren M, Creager RL, et al.. “Combination therapy with thymosin alpha 1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial.” Hepatology. 1998. 27(4):1128–1135 DOI PubMedRCT

   Well-designed double-blind RCT. 109 patients. Ta1 + IFN showed modest benefit over IFN alone. Now largely academic given DAA revolution.

10. [10]

    Andreone P, Cursaro C, Gramenzi A, et al.. “Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.” J Viral Hepat. 2004. 11(1):69–73 DOI PubMedPilot study

    Small pilot RCT (n=41). Showed significant benefit of combination therapy. Limited by sample size.

11. [11]

    Shang W, Zhang B, Ren Y, et al.. “Thymosin alpha1 use in adult COVID-19 patients: A systematic review and meta-analysis on clinical outcomes.” Int Immunopharmacol. 2022. 114:109584 DOISystematic review

    Largest COVID-19 meta-analysis (9 studies, 5,352 patients). Found no overall mortality benefit. Methodologically sound.

12. [12]

    Liu J, Shen Y, Wen Z, Xu Q, Wu Z, et al.. “Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study.” Front Immunol. 2021. 12:673693 DOI PubMedRCT

    Multicenter cohort study. Found Ta1 associated with worse outcomes in severe COVID but potentially better outcomes when used early. Important nuance for timing of administration.

13. [13]

    Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI. “The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.” Inflammopharmacology. 2023. 31(6):3317–3325 DOISystematic review

    Focused on moderate-to-critical patients. Found significant mortality reduction but no difference in ventilation needs or hospital stay.

14. [14]

    Li C, Bo L, Liu Q, Jin F. “Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis.” Int J Infect Dis. 2015. 33:90–96 DOI PubMedSystematic review

    Well-conducted meta-analysis of 6 RCTs. Significant mortality reduction (RR 0.59, p=0.0001). Predominantly Chinese ICU studies.

15. [15]

    Liu F, Wang HM, Wang T, Zhang YM, Zhu X. “The efficacy of thymosin alpha 1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials.” BMC Infect Dis. 2016. 16:488 DOISystematic review

    Systematic review of 10 RCTs (530 patients). Confirmed mortality reduction. Similar limitations — predominantly Chinese trials.

16. [16]

    Costantini C, Bellet MM, Pariano M, et al.. “A reappraisal of thymosin alpha1 in cancer therapy.” Front Oncol. 2019. 9:873 DOIReview

    Comprehensive review of Ta1 in oncology. Covers M2-to-M1 macrophage polarization, dendritic cell activation, and clinical data in melanoma, HCC, and NSCLC.

17. [17]

    Ciancio A, Rizzetto M. “Thymosin alpha-1 in the treatment of hepatocellular carcinoma.” Ann N Y Acad Sci. 2012. 1270:56–61 DOIReview

    Review of Ta1 in HCC. Reports improved outcomes when combined with chemoembolization.

18. [18]

    Dinetz E, Lee R, et al.. “Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials.” Altern Ther Health Med. 2024. 30(1):6–12 PubMedSystematic review

    Most comprehensive recent review. 11,000+ subjects across 30+ trials. Concludes Ta1 is well-tolerated and effective. Published in a complementary medicine journal, which may affect reception.

19. [19]

    Tuthill C, Rios I, McBeath R. “Thymosin alpha 1: A comprehensive review of the literature.” World J Virol. 2020. 9(5):67–78 DOIReview

    Broad review covering history, mechanism, clinical applications. Note: authors are affiliated with SciClone Pharmaceuticals (Zadaxin manufacturer) — potential COI.

20. [20]

    U.S. Food and Drug Administration. “Pharmacy Compounding Advisory Committee Meeting — Thymosin Alpha-1 (December 4, 2024).” 2024. Link

    PCAC voted against including Ta1 on the 503A bulks list. Recommendation only — formal rulemaking still required.

21. [21]

    World Anti-Doping Agency. “The 2026 Prohibited List — International Standard.” 2026. Link

    Thymosin alpha-1 is not explicitly named. Thymosin beta-4 derivatives are prohibited under S2.3. Ta1's status is ambiguous under the broad 'other growth factors' clause.

22. [22]

    TESTS trial investigators. “The efficacy and safety of thymosin alpha1 for sepsis (TESTS): a multicentre, double blind, randomised, placebo controlled, phase 3 trial.” BMJ. 2025. PubMedRCT

    Largest, most rigorous sepsis RCT for thymosin alpha-1; null primary result (HR 0.99, P=0.93).

23. [23]

    Gu B, Zhou Y, Nie Y, Wang L, Liang L, Liao Z, et al.. “Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.” Front Cell Infect Microbiol. 2025. 15:1673959 DOI PubMedSystematic review

    11 RCTs, 1,927 patients (967 treatment / 960 control), TESTS included. The headline pooled result is positive — 28-day mortality OR 0.73 (95% CI 0.59-0.90, P=0.003) — but it does not survive the authors' own sensitivity analyses: restricted to high-quality trials the estimate is OR 0.82 (95% CI 0.65-1.03, P=0.09), and restricted to multicentre trials OR 0.86 (95% CI 0.68-1.08, P=0.20). Trial sequential analysis indicates the accumulated sample size is still inadequate. This is why the positive pooled estimate does not overturn the null TESTS result.

24. [24]

    Kang X, Wang S, Zhang L, et al.. “Thymosin Alpha-1 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis.” Advanced Science. 2026.:e22372 DOI PubMedAnimal study

    Peer-reviewed cell and mouse ischemic-stroke study proposing HCRTR1/RIPK3-mediated neuroprotection. It includes a small human biomarker observation, not a human therapeutic intervention.

25. [25]

    Wei Y, Chen J, Zhang Y, et al.. “Thymosin Alpha-1 Restores Chemotherapy-Induced Antitumor Immunity by Chaperoning a MicroRNA Ligand of TLR7 in Dendritic Cells.” Cancer Research. 2026. 86(17):4238–4254 DOI PubMedAnimal study

    Peer-reviewed cell and mouse tumor-model study proposing a miR-146a-5p/TLR7 dendritic-cell mechanism. Its therapeutic efficacy experiments were not conducted in people.

26. [26]

    Kim SD, Kim KR, Kim DH, et al.. “Clinical Applications and Evidence Landscape of Thymosin Alpha 1 as an Immunomodulatory Adjunct in Cancer Care: A Scoping Review.” Pharmaceuticals (Basel). 2026. DOI PubMedReview

    Scoping review of 26 clinical publications, predominantly retrospective studies and case reports. Heterogeneous treatment settings and inconsistent safety reporting; no causal attribution from the reported combination-treatment toxicity case.

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