Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges

Table 6 Emerging immunotherapies in autism spectrum disorder

Intervention	Ref.	Population	Key findings	Status/safety
Low-dose IL-2	Case reports/series (Chen et al[159] in 2025, Li et al[253] in 2024)	Small N (children)	Positive: Improvements in speech, social interaction, sleep. Mechanism: Corrected Th1/Treg immune imbalance	Experimental. No adverse events reported in these cases
M2 macrophage secretome	Clinical trial (Shevela et al[171], 2024)	n = 71 (3-13 years)	Positive: Reduced language impairment and autistic-like behavior via intranasal delivery	Experimental. Reported as safe and well-tolerated
GcMAF	In vitro study (Siniscalco et al[172], 2014)	Macrophage cells	Mechanistic: Normalized endocannabinoid gene expression in cells	Unproven/risky. Unlicensed; no clinical evidence provided
Allergy immunotherapy	Case report (Sood et al[174], 2016)	n = 1 (8 years)	Feasibility: Behavioral strategies allowed successful treatment of comorbid allergies	Standard therapy for atopy (not ASD core symptoms)

Table 6 presents highly experimental and emerging immunotherapies for autism spectrum disorder, based on the hypothesis that a subset of autism spectrum disorder is driven by immune dysregulation or neuroinflammation. The current evidence base is extremely low certainty, relying primarily on case reports/series and preclinical studies rather than large-scale randomized controlled trials. Low-dose interleukin-2 and the M2 macrophage secretome show POSITIVE initial signals in small human trials, demonstrating improvements in symptoms like speech, social interaction, and language impairment. The mechanism is hypothesized to involve correcting the imbalance between Th1 and Treg cells. These interventions are highly experimental but have been reported as safe in the limited cases studied. Gc protein-derived macrophage activating factor is listed primarily for its mechanistic interest (in vitro), but it is generally considered unproven and risky due to a lack of clinical evidence and issues surrounding its licensing and production. Allergy immunotherapy is relevant for treating comorbid atopy (allergies), not core autism spectrum disorder symptoms, though managing comorbidities can indirectly improve behavior. Overall, these interventions target specific biological pathways (e.g., T-cell differentiation, macrophage function) that are hypothesized to be dysfunctional in autism spectrum disorder, but they remain far from clinical recommendation and require extensive, rigorous double-blind randomized controlled trial validation. IL-2: Interleukin-2 (a type of cytokine); M2 macrophage: A type of macrophage (immune cell) associated with tissue repair and anti-inflammation; GcMAF: Gc protein-derived macrophage activating factor; Th1: T helper type 1 cell (an immune cell); Treg: Regulatory T cell (an immune cell that suppresses immune responses); In vitro: Experiment performed in a test tube or culture dish (outside a living organism); ASD: Autism spectrum disorder.