Method for the Treatment of a Solid Tumour

Abstract

The present invention relates generally to a method of treating a neoplastic condition and to agents useful for same. More particularly, the present invention is directed to a method of facilitating the treatment of a solid tumor in a localised manner via the co-administration of particulate material and a cellular toxin. The method of the present invention is useful in a range of therapeutic treatments including the treatment of primary and metastatic tumors.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to a method of treating a neoplastic condition and to agents useful for same. More particularly, the present invention is directed to a method of facilitating the treatment of a solid tumour in a localised manner via the co-administration of particulate material and a cellular toxin. The method of the present invention is useful in a range of therapeutic treatments including the treatment of primary and metastatic tumours.BACKGROUND OF THE INVENTION[0002]Bibliographic details of the publications referred to by the author in this specification are collected alphabetically at the end of the description.[0003]The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the ...

AI Technical Summary

Problems solved by technology

As treatments for infectious diseases and the prevention of cardiovascular disease continues to improve, and the average life expectancy increases, cancer is likely to become the most common fatal disease in these countries.

However, immunological approaches to the treatment of cancer have been attempted for over a century with unsustainable results.

Further, these treatments are associated with severe side effects including disfigurement and scarring from surgery (e.g. mastectomy or limb amputation), severe nausea and vomiting from chemotherapy, and most significantly, the damage to normal tissues such as the hair follicles, gut and bone marrow which is induced as a result of the relatively non-specific targeting mechanism of the toxic drugs which form part of most cancer treatments and is a major limiting factor for dosage

The rapid growth and poor vascular development of most solid tumours puts many tumour cells well beyond the capacity of the drugs to penetrate the tissue.

Solid tumours are not usually curable once they have spread or ‘metastasised’ throughout the body.

Nonetheless, even at this early stage, and particularly if the tumour has spread to the draining lymph nodes, microscopic deposits of cancer known as micrometastases may have already spread throughout the body and will subsequently lead to the death of the patient.

Although radiosensitising drugs increase tumour response, they also increase toxicity to adjacent normal tissues, which is especially true of the potent new generation radiosensitisers, gemcitabine and docetaxel.

Nonetheless, the efficiency of RIT as a treatment for solid tumours may be hampered by the low penetration of antibody through the tissue barriers that surround the target antigen in the tumour, which will consequently extend circulatory half life of the antibody (Britz-Cunningham et al.

Furthermore, RIT is often impeded by the heterogeneity of the target antigen's expression within the tumour.

Thus, although RIT affords molecular targeting of tumour cells, the major limitation of RIT remains the toxicity that may result from large doses of radiation that are delivered systemically in order to achieve sufficient targeting (Britz-Cunningham et al.

Altogether, a useful therapeutic index using RIT has proven difficult to achieve clinically (Sellers et al.

Although abundant ubiquitous antigens may provide a more concentrated and accessible target for RIT, studies adopting this have been extremely limited.

However, although previous attempts at using particulate material, such as nanoparticles, to target tumours for either diagnostic or therapeutic purposes have been extensive, in the context of therapeutics there has, disappointingly, been minimal success.

However, in terms of the delivery of a therapeutic agent, such shallow penetration has not been sufficient to effectively deliver the agent throughout the tumour, in particular to the interior of the tumour, as is required if total tumour destruction is to be achieved.

In relation to therapeutics, specifically, conjugation of particles to a wide variety of different materials has so far failed to live up to the promise of achieving effective tumour penetration, this being an essential prerequisite for a therapeutic to have any chance of effectiveness.

These newly formed tumour vessels are usually abnormal in form and architecture.

Furthermore, tumour tissues usually lack effective lymphatic drainage.

All these factors will lead to abnormal molecular and fluid transport dynamics, especially for macromolecular drugs.

Often they cannot penetrate the tight endothelial junctions of normal blood vessels, but they can extravasate in tumour vasculature and become trapped in the tumour vicinity.

Nevertheless, the EPR effect has not been efficiently or successfully harnessed.

However, even if this is achievable, the issue of tissue penetration is still a separate one which, to date, has not been successfully overcome.

The general notion of the use of a nanoparticle as a vector for delivery of a drug is widely discussed in the literature but, in the absence of achieving deep tumour penetration, is of limited value.

Even where effective tumour distribution of a drug is achieved (by whatever means) a further problem has been the fact that neoplastic cells within solid tumours can exhibit a slowed metabolism.

This means that even if a cytotoxic drug penetrates to these cells, if it is not effectively metabolised it will have a limited impact on the viability of the tumour.

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