Nanoparticles — particles in the size range 1–100 nm — are emerging as a class of therapeutics for cancer. Early clinical results suggest that nanoparticle therapeutics can
show enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumours and active cellular uptake. Here, we
highlight the features of nanoparticle therapeutics that distinguish them from previous anticancer therapies, and describe how these features provide the potential for
therapeutic effects that are not achievable with other modalities. While large numbers of preclinical studies have been published, the emphasis here is placed on preclinical and clinical studies that are likely to affect clinical investigations and their implications for advancing the treatment of patients with cancer.

Nanoparticle therapeutics: an emerging treatment modality for cancer

A murine monoclonal antibody specific for calf intestinal alkaline phosphatase has been prepared and used in an unlabeled antibody bridge technique for labeling monoclonal antibodies. This procedure--the alkaline phosphatase monoclonal anti-alkaline phosphatase (APAAP) method--gives excellent immunocytochemical labeling of tissue sections and cell smears, comparable in clarity and intensity to that achieved with immunoperoxidase labeling. If the enzyme label is developed with a naphthol salt as a coupling agent and Fast Red or hexazotized new fuchsin as a capture agent, a vivid red reaction product is obtained which is very easily detected by the human eye. For this reason the APAAP technique was found particularly suitable for labeling cell smears (for both cytoplasmic and surface-membrane antigens) and for detecting low numbers of antigen-bearing cells in a specimen (e.g., carcinoma cells in a malignant effusion). It was found possible to enhance the intensity of the APAAP labeling reaction substantially by repeating the second and third incubation steps (i.e., the unlabelled "bridge" antibody and APAAP complexes). The APAAP technique was superior to immunoperoxidase labeling for staining tissues rich in endogenous peroxidase, and could be used in conjunction with immunoperoxidase methods for double immunoenzymatic staining. The method was also applicable to the detection of antigenic molecules following their electrophoretic transfer from SDS-polyacrylamide gels to nitrocellulose sheets ("immunoblotting").

Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes).

A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma study group

Background DNA fragments that appeared to belong to an unidentified human herpesvirus were recently found in more than 90 percent of Kaposi's sarcoma lesions associated with the acquired immunodeficiency syndrome (AIDS). These fragments were also found in 6 of 39 tissue samples without Kaposi's sarcoma, including 3 malignant lymphomas, from patients with AIDS, but not in samples from patients without AIDS. Methods We examined the DNA of 193 lymphomas from 42 patients with AIDS and 151 patients who did not have AIDS. We searched the DNA for sequences of Kaposi's sarcoma–associated herpesvirus (KSHV) by Southern blot hybridization, the polymerase chain reaction (PCR), or both. The PCR products in the positive samples were sequenced and compared with the KSHV sequences in Kaposi's sarcoma tissues from patients with AIDS. Results KSHV sequences were identified in eight lymphomas in patients infected with the human immunodeficiency virus. All eight, and only these eight, were body-cavity–based lymphomas — that...

Kaposi's Sarcoma–Associated Herpesvirus-Like DNA Sequences in AIDS-Related Body-Cavity–Based Lymphomas

Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia.

The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen.

https://jcp.bmj.com/content/jclinpath/39/5/547.full.pdf

Reactivity of T lymphotropic retrovirus antibody (12/1-2) in man: comparison of epidermis with other epithelial cells.

The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells [corrected and republished with original paging, article originally printed in J Immunol 1991 Oct 15;147(8):2474-82]

Skin biopsies from 150 patients with cutaneous lymphoma, premalignant or “pseudolymphomatous” conditions and benign dermatoses were examined by immunoenzymatic staining of frozen sections with a panel of monoclonal antibodies against lymphocytes, macrophages and accessory cells. Two patterns of infiltration were identified. In one of these T cells associated with Langerhans cells and HLA-DR-positive macrophages of dendritic morphology, were seen. In the other B cell follicles were present in addition to the above type of infiltrate. The latter pattern was restricted to patch tests biopsies, cutaneous lymphocytomas, and malignant lymphomas of B-cell origin.

Benign and Malignant Lymphocytic Skin Infiltrates Immunological Patterns Recognized by Immunohistochemical Staining with Monoclonal Antibodies

Sixty-four cases of mainly lymphoid lesions were investigated by fine needle aspiration. Both conventional smears and cytospin preparations were made from this material. Diagnoses based on cytological and immunocytological criteria were made in 57 of these cases and include reactive hyperplasia, non-Hodgkin's and Hodgkin's lymphoma and metastatic carcinoma. Five cases were inadequate for diagnostic purposes and in 2 cases no definite diagnosis could be made. These diagnoses were confirmed using tissue sections in 48/51 cases (with only 3 cytological diagnoses significantly altered by histology) and supported by supplementary clinical information in 8 cases. These results demonstrate the value of FNA biopsy in the investigation of lymphoid lesions using both conventional cytology and immunocytochemistry.

Immunocytochemical Analysis of Lymphoid Lesions Using -Fine Needle Aspiration Biopsy

Improved detection of common translocation breakpoints in non-Hodgkins lymphomas by fluorescence in situ hybridization on routine paraffin embedded tissue samples.

D Y Mason

Papers

Reactivity of T lymphotropic retrovirus antibody (12/1-2) in man: comparison of epidermis with other epithelial cells.

The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells [corrected and republished with original paging, article originally printed in J Immunol 1991 Oct 15;147(8):2474-82]

Benign and Malignant Lymphocytic Skin Infiltrates Immunological Patterns Recognized by Immunohistochemical Staining with Monoclonal Antibodies

Immunocytochemical Analysis of Lymphoid Lesions Using -Fine Needle Aspiration Biopsy

Improved detection of common translocation breakpoints in non-Hodgkins lymphomas by fluorescence in situ hybridization on routine paraffin embedded tissue samples.