In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's “magic bullets” to a modern age “guided missile”. In the recent years of immunologic research we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anti-cancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology, have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, to regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals; monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and high affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. Distinct from conventional monoclonal approaches that only attack cell surface associated proteins which account for only 20% of human proteins, AIT technology now addresses the far more abundant intracellular proteome. The combination of these features open up entirely new vistas for the treatment of many different kinds of cancer.





Melanoma is the most aggressive form of skin cancer, and the most common cancer in men and women ages 20-29. Over the past several decades, the incidence of melanoma has steadily increased in the United States, with the number of cases more than doubling in the past 20 years alone. If caught in the earliest stages, melanoma is entirely treatable with a very high survival rate. If untreated and allowed to spread, there is no good treatment or cure. .

AIT identifies p/MHC complexes that are expressed at high levels on the surface of melanoma cells. This high level expression was validated by direct biochemical means through the elution of this peptide from the surface of melanoma cells and its quantitative analysis by mass spectroscopy and directly by specific TCRL antibodies. AIT's Melanoma-specific TCRL antibody binds to human melanoma target cells with high intensity and high specificity, inducing significant destruction of these cells.








Anti-Viral Therapies and TCRLs

AIT's TCRL antibodies are designed to be highly specific, and thus targeted, to virus-infected cells, destroying only those cells and sparing uninfected cells. In contrast to current viro-static therapies, which only limit viral growth temporarily, and thus require chronic, and possibly lifelong administration, TCRL therapy is potentially viro-cidal, destroying and eliminating all residuals of the virus infected cells, and thus requiring only a finite and limited number of treatments.

Of all the human herpes viruses described to date, infection with CMV is considered to be the most important cause of morbidity and mortality. Approximately 70% of the world population are carriers of the virus, and several high risk groups, including immuno-compromised organ transplant recipients and individuals infected with HIV, are at risk of developing life threatening CMV disease due to its reactivation.

While immunity to CMV is complex, studies have shown that CTLs are of major importance in the prevention of recurrence. The highly expressed viral protein pp65 has been shown to be the primary target of the CTL-mediated immune response. AIT has demonstrated that TCRL antibodies targeted to HLA-A2 in complex with the pp65 peptide, can recognize, bind, and destroy CMV-infected human cells.




The human T-cell lymphotropic virus type I (HTLV-I) is an exogenous human retrovirus which infects approximately 10 – 20 million people worldwide. Although the majority of infected individuals remain healthy and asymptomatic, approximately 1-3% of carriers develop an inflammatory disease of the central nervous system termed HTLV-I-associated myelopathy / tropical spastic paraparesis (HAM/TSP). HTLV-I is also the etiologic agent in adult T-cell leukemia (ATL), and other inflammatory diseases.

One of the most remarkable features of the cellular immune response in HAM/TSP patients is the highly elevated levels of HTLV-I-specific CTLs, and more specifically, CTLs specific to the HLA-A2/Tax peptide complex.

We have demonstrated that regulatory T cells (CD4+CD25+ T cells), the major reservoir of HTLV-I pro-virus, predominantly express virus-derived Tax peptide/HLA complexes, which in turn stimulate and expand HTLV-I Tax-specific CTLs (CD8+ cytotoxic T cells). This expansion of the CTLs is important in the pathogenesis of HTLV-I associated neurological disease.

TCRL antibodies specific to HLA-A2, in complex with the HTLV-I Tax peptide, can recognize and bind exclusively to the infectedregulatory T cells and can thereforebe used for blocking the proliferation of the CTLs and the progression of infection.

TCRLs can also directly kill HTLV-1 infected cells in malignancy-induced transformation such as that which occurs in Adult T cell leukemia.









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