Immunotherapy for Infectious Diseases

Fungal Infections 315
the administration of fungal antigens to individuals with allergic sinusitis would be
harmful, a 2-year uncontrolled study revealed that it is safe and possibly beneficial
(20). A recent prospective study suggests that postoperative immunotherapy with specific
antigens to which the patient manifests sensitivity was beneficial in patients with
allergic fungal sinusitis (68).
Specific Antibody Therapy
In contrast to immunoglobulin preparations prepared from donor sera, specific antibody
therapy refers to the use of antibody preparations with high activity against specific
fungal pathogens. Examples include monoclonal antibodies (MAbs) to fungal
antigens and antibodies obtained from immunized hosts. Passive antibody therapy was
widely used in the preantibiotic era for the treatment of many bacterial and viral infections
(70,71). In recent years, there has been new interest in reintroducing passive antibody
therapy for the treatment of infectious diseases (71). Although the role of humoral
immunity in protection against fungi has been a controversial subject, it is now clear
that certain MAbs to fungal antigens can protect against experimental infection (54).
In the past, several patients with C. neoformans infections have been treated with specific
antibody (reviewed in ref. 72). Administration of specific rabbit antibodies to
patients with C. neoformans infection was well tolerated and resulted in clearance of
serum cryptococcal antigens (72). A MAb to C. neoformans capsular polysaccharide
is in advanced preclinical development, and clinical trials in patients with cryptococcosis
are expected shortly (73). For cryptococcosis, antibody therapy is envisioned as
an adjunct to antifungal therapy with the goals of reducing mortality and improving
cure rates. Protective MAbs to C. albicans have also been identified that are candidates
for clinical use (74).
ADVERSE OUTCOMES
As noted already, much of the clinical experience with immune therapy for fungal
infections consists of anecdotal case reports and small studies that usually describe
some beneficial effect. Importantly, there are also a few case reports of adverse outcomes
associated with the use of some types of immune therapy. A 10-year-old girl
developed massive fatal hemoptysis after treatment with amphotericin B and GM-CSF
for pulmonary aspergillosis (75). Given that cavitation and hemoptysis in pulmonary
aspergillosis are associated with resolution of neutropenia, this raised concern that
these complications may become more frequent as CSFs are increasingly used
to reduce neutropenia (75). Another small study reported that 2 of 12 patients
who received autologous bone marrow transplants and were treated with experimental
interleukin-12 (IL-12) immunotherapy developed fatal fungal infections, one with
Aspergillus and the other with mucor (76). Since this rate of infection was higher than
expected for autologous bone marrow recipients, the authors speculated that IL-12 therapy
may have had unintended consequences on immune function (76). In this regard,
it is noteworthy that IL-2 therapy has been associated with a fivefold increased risk
of bacteremia and Staphylococcus aureus infections, possibly because of an IL-2mediated
defect in neutrophil chemotactic function (77,78). These reports highlight the
need for controlled studies to determine the benefits and risks of immune therapy.